Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Manycultures around the world, both

ancient and modern, share beliefs in

the magical qualitiesof blood. Blood

wasconsidered the “essence oflife” be-

cause the uncontrolled lossof it can re-

sult in death. Blood was also thought to

deﬁne our character and emotions. People ofa

noble bloodline were described as“blue bloods,”

whereas criminals were considered to have “bad”

blood. It wassaid that anger caused the blood to “boil,” and fear resulted in

blood “curdling.” The scientiﬁcstudy ofblood reveals characteristics as fascinat-

ing asany of these fantasies. Blood performsmany functions essential to life and

often can revealmuch about our health.

Bloodis a type of connective tissue, consisting of cellsand cell fragments

surrounded bya liquid matrix. The cells and cell fragments are the formed ele-

ments, and the liquid isthe plasma. The formed elements make up about 45%,

and plasma makesup about 55% of the total blood volume (ﬁgure 19.1). The to-

tal blood volume in the average adultis about 4-5 L in females and 5-6 L in

males. Blood makesup about 8% of the total weight of the body.

Cellsrequire constantnutrition and waste removal because they are meta-

bolicallyactive. The cardiovascular system, which consists of the heart, blood

vessels, and blood, connectsthe various tissues of the body. The heart pumps

blood through blood vessels, and the blood deliversnutrientsand picks up waste

products.

Thischapter explains the functions of blood (640), plasma (641), and the

formed elements(642) of blood. Hemostasis (650),blood grouping (655), and di-

agnosticblood tests (658) are also described.

Cardiovascular

System

Blood

Colorized scanning electron micrograph (SEM) of

a blood clot. The red discsare red blood cells, the

blue particlesare platelets, and the yellowstrands

are ﬁbrin.

CHAPTER

Part 4 Regulationsand Maintenance

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Percentage by

body weight

Percentage by

volume

Other fluids

and tissues 92%

Plasma

55%

Blood

Formed

elements

45%

Plasma

(percentage by weight)

Formed elements

(number per cubic mm)

Platelets

250–400 thousand

White blood cells

5–9 thousand

Red blood cells

4.2–6.2 million

Proteins 7%

Water

91%

Other solutes 2%

Albumins

58%

Globulins

38%

Fibrinogen

Ions

Nutrients

Waste products

Gases

Regulatory

substances

White blood cells

Neutrophils

60%–70%

Lymphocytes

20%–25%

Monocytes

3%–8%

Eosinophils

2%–4%

Basophils

0.5%– 1%

Figure 19.1

Composition ofBlood

Approximate valuesfor the components of blood in a normaladult.

Functions of Blood

Objective

■ Explain the functionsof the blood.

Blood is pumped by the heart through blood vessels,which

extend throughout the body.Blood helps to maintain homeostasis

in several ways.

1. Transport ofgases,nutrients, and waste products. Oxygen

enters blood in the lungs and is carried to cells.Carbon

dioxide,produced by cells, is carried in the blood to the

lungs,from which it is expelled. Ingested nutrients, ions,

and water are transported by the blood from the digestive

Part4 Regulationsand Maintenance640

tract to cells,and waste products of cells are transported by

the blood to the kidneys for elimination.

2. Transport ofprocessed molecules.Many substances are

produced in one part ofthe body and transported in the

blood to another part where they are modiﬁed.For example,

the precursor to vitamin D is produced in the skin (see

chapter 5) and transported by the blood to the liver and then

to the kidneys for processing into active vitaminD. Active

vitamin D is transported in the blood to the small intestines,

where it promotes the uptake ofcalcium. Another example

is lactic acid produced by skeletal muscles during anaerobic

respiration (see chapter 9).Lactic acid is carried by the blood

to the liver,where it is converted into glucose.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Chapter 19 Cardiovascular System: Blood 641

3. Transport ofregulatory molecules.Many of the hormones

and enzymes that regulate body processes are carried from

one part ofthe body to another by the blood.

4. Regulation ofpH and osmosis. Buffers (see chapter 2),which

help keep the blood’s pH within its normal limits of

7.35–7.45,are in the blood. The osmotic composition of

blood is also critical for maintaining normal ﬂuid and ion

balance.

5. Maintenance ofbody temperature.Blood is involved with

body temperature regulation because warm blood is

transported from the interior to the surface ofthe body,

where heat is released from the blood.

6. Protection against foreign substances.Cells and chemicals of

the blood make up an important part ofthe immune

system,protecting against foreign substances such as

microorganisms and toxins.

7. Clot formation.Blood clotting provides protection against

excessive blood loss when blood vessels are damaged.When

tissues are damaged,the blood clot that forms is also the

ﬁrst step in tissue repair and the restoration ofnormal

function (see chapter 4).

1. List the ways that blood helps to maintain homeostasis in

the body.

Plasma

Objective

■ Listthe components of blood plasma, and explain their

functions.

Plasma(plaz⬘ma˘) is the liquid part ofblood. It’s a pale yel-

low ﬂuid that consists of about 91% water and 9% other sub-

stances, such as proteins, ions, nutrients, gases, and waste

products (table 19.1). Plasma is a colloid (kol⬘oyd), which is a

liquid containing suspended substances that don’t settle out of

solution.Most of the suspended substances are plasma proteins,

which include albumin, globulins, and fibrinogen. Albumin

Table 19.1

Plasma Components Function

Water Acts as a solvent and suspending medium for blood components

Plasma Proteins

Albumin Partly responsible for blood viscosity and osmotic pressure; acts as a buffer; transports fatty acids,

free bilirubin, and thyroid hormones

Globulins Transports lipids, carbohydrates, hormones, and ions like iron and copper; antibodies and

complement are involved in immunity

Fibrinogen Functions in blood clotting

Ions

Sodium, potassium, calcium, Involved in osmosis, membrane potentials, and acid–base balance

magnesium, chloride, iron,

phosphate, hydrogen, hydroxide,

bicarbonate

Nutrients

Glucose, amino acids, triacylglycerol, Source of energy and basic "building blocks" of more complex molecules

cholesterol

Vitamins Promote enzyme activity

Waste Products

Urea, uric acid, creatinine, Breakdown products of protein metabolism; excreted by the kidneys

ammonia salts

Bilirubin Breakdown product of red blood cells; excreted as part of the bile from the liver into the intestine

Lactic acid End product of anaerobic respiration; converted to glucose by the liver

Gases

Oxygen Necessary for aerobic respiration; terminal electron acceptor in electron-transport chain

Carbon dioxide Waste product of aerobic respiration; as bicarbonate, helps buffer blood

Nitrogen Inert

Regulatory Substances Enzymes catalyze chemical reactions; hormones stimulate or inhibit many body functions

Composition of Plasma

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

(al-bu¯⬘min) makes up 58% ofthe plasma proteins and is impor-

tant in the regulation of water movement between tissues and

blood. Because albumin doesn’t easily pass from the blood into

tissues, it plays an important role in maintaining the osmotic

concentration of blood (see chapters 3 and 26). Globulins

(glob⬘u¯-linz) account for 38% ofthe plasma proteins.Some glob-

ulins, such as antibodies and complement, are part of the im-

mune system (see chapter 22), whereas others function as

transport molecules (see chapter 17).Fibrinogen (f ı¯-brin⬘o¯-jen)

constitutes 4% of the plasma proteins and is responsible for the

formation ofblood clots (see “Coagulation” on p. 651).

The water,proteins, and other substances in the blood, such

as ions,nutrients, waste products, gases,and regulatory substances,

are maintained within narrow limits. Normally, water intake

through the digestive tract closely matches water loss through the

kidneys,lungs, digestive tract, and skin. Therefore, plasma volume

remains relatively constant.Suspended or dissolved substances in

the blood come from the liver, kidneys, intestines,endocrine

glands,and immune tissues like the spleen. Oxygen enters blood in

the lungs and leaves the blood as it ﬂows through tissues.Carbon

Part4 Regulationsand Maintenance642

dioxide enters blood from the tissues and leaves the blood as it

ﬂows through the lungs.

2. Deﬁne the term plasma. What are the functions of albumin,

globulins, and ﬁbrinogen in plasma? Whatother

substancesare found in plasma?

Formed Elements

Objectives

■ Describe the origin and formation of the formed elements.

■ Describe the structure, function, production, and

breakdown of red blood cells.

■ Describe the structuresand functions of white blood cells

and platelets.

About 95% of the volume of the formed elements consists

of red blood cells, or erythrocytes (e˘-rith⬘ro¯-sı¯tz). The remaining

5% consists of white blood cells, or leukocytes (loo⬘ko¯-sı¯tz),and

cell fragments called platelets, or thrombocytes (throm⬘bo¯-sı¯tz).

Table 19.2

CellType Illustration Description Function

Red blood cell Biconcave disk; no nucleus; contains Transports oxygen and carbon dioxide

hemoglobin, which colors the cell red;

7.5µm in diameter

White blood cell Spherical cell with a nucleus; white in color Five types of white blood cells, each with specific

because it lacks hemoglobin functions

Granulocytes

Neutrophil Nucleus with two to four lobes connected Phagocytizes microorganisms and other

bythin filaments; cytoplasmic granules substances

stain a light pink or reddish purple;

10–12µm in diameter

Basophil Nucleus with two indistinct lobes; cytoplasmic Releases histamine, which promotes inflammation,

granules stain blue-purple; 10–12µm and heparin, which prevents clot formation

in diameter

Eosinophil Nucleus often bilobed; cytoplasmic granules Releases chemicals that reduce inflammation;

stain orange-red or bright red; attacks certain worm parasites

11–14µm in diameter

Agranulocytes

Lymphocyte Round nucleus; cytoplasm forms a thin ring Produces antibodies and other chemicals

around the nucleus; 6–14µm in diameter responsible for destroying microorganisms;

contributes to allergic reactions, graft rejection,

tumor control, and regulation of the immune

system

Monocyte Nucleus round, kidney-shaped, or horseshoe- Phagocytic cell in the blood; leaves the blood

shaped; contains more cytoplasm than and becomes a macrophage, which

does lymphocyte; 12–20µm in diameter phagocytizes bacteria, dead cells, cell

fragments, and other debris within tissues

Platelet Cell fragment surrounded by a plasma Forms platelet plugs; releases chemicals

membrane and containing granules; necessary for blood clotting

2–4µm in diameter

Formed Elements of the Blood

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Chapter 19 Cardiovascular System: Blood 643

The formed elements of the blood are outlined and illustrated in

table 19.2.In healthy adults, white blood cells are the only formed

elements possessing nuclei, whereas red blood cells and platelets

lack nuclei.

White blood cells are named according to their appearance

in stained preparations.Granulocy tes (gran⬘yu¯-lo¯-sı¯tz) are white

blood cells with large cytoplasmic granules and lobed nuclei (see

table 19.2).Their granules stain with dyes that make the cells more

visible when viewed through a light microscope.The three types of

granulocytes are named according to the staining characteristics of

their granules:neutrophils (nu⬘tro¯-ﬁlz) stain with acidic and basic

dyes, eosinophils (e¯-o¯-sin⬘o¯-ﬁlz) stain with acidic dyes, and ba-

sophils (ba¯⬘so¯-ﬁlz) stain with basic dyes. Agranulocytes

(a˘-gran⬘yu¯-lo¯-sı¯tz) are white blood cells that appear to have no

granules when viewed in the light microscope.Agranulocytes actu-

ally have granules,but they are so small that they cannot be seen

easily with the light microscope. The two types of agranulocytes

are monocytes(mon⬘o¯-sı¯tz) and lymphocytes (lim⬘fo¯-sı¯tz). They

have nuclei that are not lobed.

Production ofFormed Elements

The process of blood cell production, called hematopoiesis

(he¯⬘ma˘-to¯-poy-e¯⬘sis, hem´a˘-to-poy-e¯⬘sis) or hemopoiesis(he¯⬘mo¯-

poy-e¯⬘sis), occurs in the embryo and fetus in tissues like the yolk

sac,liver, thymus, spleen, lymph nodes, and red bone marrow.Af-

ter birth,hematopoiesis is conﬁned primarily to red bone marrow,

with some lymphoid tissue helping in the production of lympho-

cytes (see chapter 22).In young children, nearly all the marrow is

red bone marrow.In adults,however, red marrow is conﬁned to the

ribs, sternum, vertebrae, pelvis, proximal femur,and proximal

humerus.Yellow marrow replaces red marrow in other locations in

the body (see chapter 6).

All the formed elements ofthe blood are derived from a sin-

gle population of stem cells located in the red bone marrow.He-

mopoietic stem cells are precursor cells capable of dividing to

produce daughter cells that can differentiate into various types of

blood cells (ﬁgure 19.2): proerythroblasts (pro¯-e˘-rith⬘ro¯-blastz),

from which red blood cells develop;myeloblasts (mı¯⬘e˘-lo¯-blastz),

from which basophils,eosinophils, and neutrophils develop; lym-

phoblasts (lim⬘fo¯-blastz), from which lymphocytes develop;

monoblasts(mon⬘o¯-blastz),from which monocytes develop; and

megakaryoblasts(meg-a˘-kar⬘e¯-o¯-blastz), from which platelets de-

velop.The development of the cell lines is regulated by growth fac-

tors. That is, the type of formed element derived from the stem

cells and how many formed elements are produced are determined

by different growth factors.

3. Name the three general types of formed elements in the

blood.

4. Deﬁne hematopoiesis. What is a stem cell? What types of

formed elementsdevelop from proerythroblasts,

myeloblasts, lymphoblasts, monoblasts, and

megakaryoblasts?

Stem Cellsand Cancer Therapy

Manycancer therapies affect dividing cells, such asthose found in

tumors. An undesirable side effectof such therapies, however, can be

the destruction ofnontumor cells that are dividing, such asthe stem

cellsand their derivatives in red bone marrow. After treatment for cancer,

growth factorsare used to stimulate the rapid regeneration of the red

bone marrow. Although nota cure for cancer, the use of growth factors

can speed recoveryfrom the cancer therapy.

Some typesof leukemia and genetic immune deﬁciency diseases

can be treated with a bone marrow or stem celltransplant. To avoid

problemsof tissue rejection, families with a history of these disorders

can freeze the umbilicalcord blood of their newborn children. The cord

blood containsmany stem cells and can be used instead ofa bone

marrow transplant.

Red Blood Cells

Red blood cells,or er ythrocytes, are about 700 times more numer-

ous than white blood cells and 17 times more numerous than platelets

in the blood (ﬁgure 19.3a).Males have about 5.4 million red blood

cells per microliter (␮L;1 mm

or 10

⫺6

L) of blood (range: 4.6–6.2

million),whereas females have about 4.8 million/␮L (range: 4.2–5.4

million). Red blood cells cannot move oftheir own accord and are

passively moved by forces that cause the blood to circulate.

Structure

Normal red blood cells are biconcave disks about 7.5 ␮m in diam-

eter with edges that are thicker than the center of the cell (ﬁgure

19.3b). Compared to a ﬂat disk of the same size, the biconcave

shape increases the surface area of the red blood cell.The greater

surface area makes the movement ofgases into and out of the red

blood cell more rapid.In addition, the red blood cell can bend or

fold around its thin center,thereby decreasing its size and enabling

it to pass more easily through small blood vessels.

Red blood cells are derived from specialized cells that lose

their nuclei and nearly all their cellular organelles during matura-

tion.The main component of the red blood cell is the pigmented

protein hemoglobin (he¯-mo¯-glo¯⬘bin),which occupies about one-

third of the total cell volume and accounts for its red color.Other

red blood cell contents include lipids, adenosine triphosphate

(ATP),and the enzyme carbonic anhydrase.

Function

The primary functions of red blood cells are to transport oxygen

from the lungs to the various tissues of the body and to transport

carbon dioxide from the tissues to the lungs.Approximately 98.5%

ofthe oxygen transported in the blood is tr ansported in combina-

tion with the hemoglobin in the red blood cells,and the remaining

1.5% is dissolved in the water part ofthe plasma. If red blood cells

rupture, the hemoglobin leaks out into the plasma and becomes

nonfunctional because the shape of the molecule changes as a re-

sult ofdenaturation (see chapter 2). Red blood cell rupture follow-

ed by hemoglobin release is called hemolysis(he¯-mol⬘i-sis).

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Part4 Regulationsand Maintenance644

Stem cell

Proerythroblast Myeloblast Lymphoblast Monoblast Megakaryoblast

Megakaryocyte

Megakaryocyte breakup

PlateletsMonocyte

LymphocyteNeutrophilEosinophil

Granulocytes Agranulocytes

White blood cells

BasophilRed blood cell

Neutrophilic

band cell

Eosinophilic

band cell

Basophilic

band cell

Neutrophilic

myelocyte

Eosinophilic

myelocyte

Progranulocyte

Basophilic

myelocyte

Early

erythroblast

Reticulocyte

Intermediate

erythroblast

Late

erythroblast

Nucleus

extruded

Figure 19.2

Hematopoiesis

Stem cellsgive rise to the cell lines thatproduce the formed elements.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Chapter 19 Cardiovascular System: Blood 645

Carbon dioxide is transported in the blood in three major

ways:approximately 7% is transported as carbon dioxide dissolved

in the plasma, approximately 23% is transported in combination

with blood proteins (mostly hemoglobin),and 70% is transported

in the form ofbicarbonate ions. The bicarbonate ions (HCO

–

) are

produced when carbon dioxide (CO

) and water (H

O) combine

to form carbonic acid (H

),which dissociates to form hydro-

gen (H

⫹

) and bicarbonate ions.The combination of carbon diox-

ide and water is catalyzed by an enzyme, carbonic anhydrase,

which is located primarily within red blood cells.

Hemoglobin

Hemoglobin consists of four polypeptide chains and four heme

groups.Each polypeptide chain, called a globin (glo¯⬘bin),is bound

to one heme (he¯m).Each heme is a red-pigment molecule con-

taining one iron atom (ﬁgure 19.4). Several types of globin exist,

Carbon

dioxide

Water

Carbonic

acid

Carbonic

anhydrase

⫹

Hydrogen

ion

HCO

⫺

Bicarbonate

ion

⫹

each having a slightly different amino acid composition.The four

globins in normal adult hemoglobin consist of two alpha (␣)

chains and two beta (␤) chains.

Embryonic and fetal hemoglobins appear at different times

during development and are replaced by adult hemoglobin near

the time of birth. Embryonic and fetal hemoglobins are more ef-

fective at binding oxygen than is adult hemoglobin.Abnormal he-

moglobins are less effective at attracting oxygen than is normal

hemoglobin and can result in anemia (see the Clinical Focus on

“Disorders ofthe Blood” on p. 660).

PREDICT

Whatwould happen to a fetus if maternal blood had an equalor

greater afﬁnityfor oxygen than does fetal blood?

Iron is necessary for the normal function ofhemoglobin be-

cause each oxygen molecule that is transported is associated with

an iron atom.The adult human body normally contains about 4 g

of iron,two-thirds of which is associated with hemog lobin.Small

amounts ofiron are regularly lost from the body in waste products

like urine and feces.Females lose additional iron as a result of men-

strual bleeding and, therefore,require more dietary iron than do

males.Dietary iron is absorbed into the circulation from the upper

part ofthe intestinal tract. Stomach acid and vitamin C in food in-

crease the absorption of iron by converting ferric iron (Fe

3⫹

) to

ferrous iron (Fe

2⫹

),which is more readily absorbed.

Effectof Carbon Monoxide on Oxygen Transport

Varioustypes of poisons affect the hemoglobin molecule. Carbon

monoxide (CO), which isproduced bythe incomplete combustion of

gasoline, bindsto the iron of hemoglobin to form the relatively stable

compound carboxyhemoglobin(kar-bok⬘se¯-he¯-mo¯-glo¯⬘bin). Asa result

ofthe stable binding of carbon monoxide, hemoglobin cannot transport

oxygen, and death mayoccur. Carbon monoxide isfound in cigarette

smoke, and the blood ofsmokers can contain 5%–15%

carboxyhemoglobin.

When hemoglobin is exposed to oxygen, one oxygen mo-

lecule can become associated with each heme group. This oxy-

genated form of hemoglobin is called oxyhemoglobin

(ok⬘se¯-he¯-mo¯-glo¯⬘bin). Hemoglobin containing no oxygen is

called deoxyhemoglobin. Oxyhemoglobin is bright red, whereas

deoxyhemoglobin has a darker red color.

Hemoglobin also transports carbon dioxide,which doesn’t

combine with the iron atoms but is attached to amino groups of

the globin molecule. This hemoglobin form is carbaminohe-

moglobin(kar-bam⬘i-no¯-he¯-mo¯-glo¯⬘bin).The transport ofoxy-

gen and carbon dioxide by the blood is discussed more fully in

chapter 23.

A recently discovered function of hemoglobin is the trans-

port of nitric oxide,which is produced by the endothelial cells lin-

ing blood vessels.In the lungs, at the same time that heme picks up

oxygen,in each ␤-globin a sulfur-containing amino acid, cysteine,

binds with a nitric oxide molecule to form S-nitrosothiol (nı¯-

tro¯s⬘o¯ -thı¯-ol;SNO).When oxygen is released in tissues so is the ni-

tric oxide, which functions as a chemical signal that induces the

smooth muscle ofblood vessels to relax. By affecting the amount of

Figure 19.3

Red Blood Cellsand White Blood Cells

(a) Scanning electron micrograph offormed elements: red blood cells (red

doughnutshapes) and white blood cells (yellow). (b) Shape and dimensions

ofa red blood cell.

7.5µm

2.0µm

Red blood

cell

White blood

cell

Top view Side view

SEM 2600x

(a)

(b)

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

nitric oxide in tissues, hemoglobin may play a role in regulating

blood pressure,because relaxation of blood vessels results in a de-

crease in blood pressure (see chapter 21).

Blood Substitutes

Currentresearch is being conducted in an attemptto develop blood

substitutesthat will deliver oxygen to tissues. One such substitute is

Hemopure. Itis an ultrapuriﬁed, chemicallycross-linked cow hemoglobin

in a balanced saltsolution. Thus, Hemopure is a stabilized hemoglobin

thatis no longer within red blood cells. The use ofHemopure for blood

transfusionshas several beneﬁtscompared to using blood. Hemopure has

a longer shelflife than blood and can be used when blood is not available.

The free oxygen-carrying hemoglobin molecule ofHemopure is 1000 times

smaller than red blood cells, thusallowing itto ﬂow past partially blocked

arteries. There are no transfusion reactionsbecause there are no red blood

cellsurface antigens (see “Blood Grouping” on p. 655). The possibilityof

transferring human diseasessuch ashepatitis or AIDS is eliminated.

Stringentmanufacturing techniques are necessary, however, to ensure the

removalof disease-causing agentsfrom cows, such as Creutzfeldt-Jakob

disease and bovine spongiform encephalopathy.

Life Historyof Red Blood Cells

Under normal conditions about 2.5 million red blood cells are de-

stroyed every second.This loss seems staggering until you realize

that it represents only 0.00001% of the total 25 trillion red blood

cells contained in the normal adult circulation.Furthermore, these

2.5 million red blood cells are replaced by an equal number ofred

blood cells every second,thus maintaining homeostasis.

The process by which new red blood cells are produced is

calleder ythropoiesis (e˘-rith⬘ro¯-poy-e¯⬘sis; see ﬁgure 19.2), and the

time required for the production ofa single red blood cell is about

4 days.Stem cells, from which all blood cells originate, give rise to

proerythroblasts. After several mitotic divisions, proerythroblasts

become early (basophilic) erythroblasts (e˘-rith⬘ro¯-blastz),which

Part4 Regulationsand Maintenance646

stain with a basic dye.The dye stains the cytoplasm a purplish color

because it binds to the large numbers ofribosomes, which are sites

of synthesis for the protein hemoglobin. Early erythroblasts give

rise to intermediate (polychromatic) erythroblasts, which stain

different colors with basic and acidic dyes.As hemoglobin is syn-

thesized and accumulates in the cytoplasm, it’s stained a reddish

color by an acidic dye.Intermediate erythroblasts continue to pro-

duce hemoglobin,and then most of their ribosomes and other or-

ganelles degenerate.The resulting late erythroblasts have a reddish

color because about one-third ofthe cytoplasm is now hemoglobin.

The late erythroblasts lose their nuclei by a process ofextru-

sion to become immature red blood cells,which are called reticu-

locytes (re-tik⬘u¯-lo¯-sı¯tz), because a reticulum, or network, can be

observed in the cytoplasm when a special staining technique is

used.The reticulum is artiﬁcially produced by the reaction of the

dye with the few remaining ribosomes in the reticulocyte.Reticu-

locytes are released from the bone marrow into the circulating

blood, which normally consists of mature red blood cells and

1%–3% reticulocytes. Within 1 to 2 days,reticulocytes become

mature red blood cells when the ribosomes degenerate.

PREDICT

Whatdoes an elevated reticulocyte count indicate? Would the

reticulocyte countchange during the week after a person had donated

a unit(about 500 mL) of blood?

Cell division requires the B vitamins folate and B

,which are

necessary for the synthesis ofDNA (see chapter 3). Hemoglobin pro-

duction requires iron.Consequently,adequate amounts of folate, vita-

min B

,and iron are necessary for normal red blood cell production.

Red blood cell production is stimulated by low blood oxygen

levels,typical causes of which are decreased numbers of red blood

cells,decreased or defective hemoglobin, diseases of the lungs, high

altitude,inability of the cardiovascular system to deliver blood to

tissues,and increased tissue demands for oxygen, for example,dur-

ing endurance exercises.

Heme

␤

␣

␤

Hemoglobin

COOH

=CH

Heme

Figure 19.4

Hemoglobin

(a) Four polypeptide chains, each with a heme, form a hemoglobin molecule. (b) Each heme containsone iron atom.

(a) (b)

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Chapter 19 Cardiovascular System: Blood 647

Low blood oxygen levels stimulate red blood cell production

by increasing the formation of the glycoprotein erythropoietin

(e˘-rith-ro¯-poy⬘e˘-tin),which is a hormone produced by the kidneys

(ﬁgure 19.5).Er ythropoietin stimulates red bone marrow to pro-

duce more red blood cells by increasing the number of pro-

erythroblasts formed and by decreasing the time required for red

blood cells to mature.Thus, when oxygen levels in the blood de-

crease, erythropoietin production increases, which increases red

blood cell production.The increased number of red blood cells in-

creases the ability of the blood to transport oxygen. This mecha-

nism returns blood oxygen levels to normal and maintains

homeostasis by increasing the delivery of oxygen to tissues.Con-

versely,if blood oxygen levels increase,less er ythropoietin is re-

leased,and red blood cell production decreases.

PREDICT

Cigarette smoke producescarbon monoxide. Ifa nonsmoker smoked a

packof cigarettes a day for a few weeks, whatwould happen to the

number ofred blood cells in the person’s blood? Explain.

Red blood cells normally stay in the circulation for about 120

days in males and 110 days in females.These cells have no nuclei

and,therefore, cannot produce new proteins.As their existing pro-

teins, enzymes,plasma membr ane components,and other struc-

tures degenerate, the red blood cells are less able to transport

oxygen and their plasma membranes become more fragile.Eventu-

ally the red blood cells rupture as they squeeze through some tight

spot in the circulation.

Macrophages located in the spleen, liver,and other lym-

phatic tissue (ﬁgure 19.6) take up the hemoglobin released from

ruptured red blood cells.Within the macrophage, lysosomal en-

zymes digest the hemoglobin to yield amino acids, iron, and

bilirubin.The globin part of hemoglobin is broken down into its

component amino acids, most of which are reused in the pro-

duction ofother proteins. Iron atoms released from heme can be

carried by the blood to red bone marrow,where they are incor-

porated into new hemoglobin molecules. The heme groups are

converted to biliverdin (bil-i-ver⬘din) and then to bilirubin

(bil-i-roo⬘bin),which is released into the plasma.Bilirubin binds

to albumin and is transported to liver cells. This bilirubin is

calledfree bilirubin because it is not yet conjugated. Free biliru-

bin is taken up by the liver cells and is conjugated,or joined, to

glucuronic acid to form conjugated bilirubin, which is more

water-soluble than free bilirubin.The conjugated bilirubin be-

comes part of the bile, which is the ﬂuid secreted from the liver

into the small intestine.In the intestine, bacteria convert biliru-

bin into the pigments that give feces its characteristic brownish

color.Some of these pigments are absorbed from the intestine,

modified in the kidneys, and excreted in the urine, thus con-

tributing to the characteristic yellowish color ofurine. Jaundice

(jawn⬘dis) is a yellowish staining of the skin and sclerae

caused by a buildup of bile pigments in the circulation and

interstitialspaces.

5. How does the shape of red blood cells contribute to their

abilityto exchange gases and move through blood vessels?

6. Give the percentage for each of the ways that oxygen and

carbon dioxide are transported in the blood. Whatis the

function of carbonicanhydrase?

7. Describe the two basic parts of a hemoglobin molecule.

Which partis associated with iron? What gases are

transported byeach part?

Decreased

blood

oxygen

Increased

blood

oxygen

Increased

erythropoietin

Increased

red blood cell

production

Red bone

marrow

Red blood cells

Kidney

Figure 19.5

Red Blood CellProduction

In response to decreased blood oxygen, the kidneysrelease erythropoietin into the generalcirculation. The increased erythropoietin stimulates red blood cell

production in the red bone marrow. Thisprocess increasesblood oxygen levels.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

8. Deﬁne erythropoiesis. Describe the formation of red blood

cells, starting with the stem cellsin the red bone marrow.

9. What is erythropoietin, where is it produced, what causes it

to be produced, and whateffect does it have on red blood

cell production?

10. Where are red blood cells removed from the blood? Listthe

three breakdown productsof hemoglobin and explain what

happensto them.

White Blood Cells

White blood cells,or leukocytes, are clear or whitish-colored cells

that lack hemoglobin but have a nucleus.In stained preparations,

white blood cells attract stain,whereas red blood cells remain rela-

tively unstained (ﬁgure 19.7;see table 19.2).

White blood cells protect the body against invading microor-

ganisms and remove dead cells and debris from the body.Most

white blood cells are motile, exhibiting ameboid movement,

which is the ability to move like an ameba by putting out irregular

cytoplasmic projections. White blood cells leave the circulation

Part4 Regulationsand Maintenance648

and enter tissues by diapedesis(dı¯⬘a˘-pe˘-de¯⬘sis),a process in which

they become thin and elongated and slip between or,in some cases,

through the cells of blood vessel walls. The white blood cells can

then be attracted to foreign materials or dead cells within the tissue

by chemotaxis (ke¯-mo¯-tak⬘sis). At the site of an infection,white

blood cells accumulate and phagocytize bacteria, dirt, and dead

cells; then they die. The accumulation of dead white blood cells

and bacteria,along with ﬂuid and cell debris, is called pus.

The ﬁve types of white blood cells are neutrophils,

eosinophils,basophils, lymphocytes, and monocytes.

Neutrophils

Neutrophils (see table 19.2), the most common type of white

blood cells in the blood,have small cytoplasmic granules that stain

with both acidic and basic dyes.Their nuclei are commonly lobed,

with the number oflobes var ying from two to ﬁve.Neutrophils are

often called polymorphonuclear (pol⬘e¯-mo¯r-fo¯-noo⬘kle¯-a˘r) neu-

trophils,or PMNs, to indicate that their nuclei can occur in more

than one (poly) form (morph). Neutrophils usually remain in the

1. The globin chains of hemoglobin

are broken down to individual

amino acids (

pink arrow

) and are

metabolized or used to build new

proteins.

2. Iron is released from the heme of

hemoglobin. The heme is

converted into biliverdin, which is

converted into bilirubin.

3. Iron is transported in combination

with transferrin in the blood to

various tissues for storage or

transported to the red bone

marrow and used in the production

of new hemoglobin (

green arrows

4. Free bilirubin (

blue arrow

) is

transported in the blood to the

liver.

5. Conjugated bilirubin is excreted as

part of the bile into the small

intestine.

6. Bilirubin derivatives contribute to

the color of feces or are

reabsorbed from the intestine into

the blood and excreted from the

kidneys in the urine.

Aged, abnormal, or

damaged red blood cells

Hemoglobin

Heme

Globin

Biliverdin

Iron

Bilirubin

Macrophage

Free bilirubin

Iron +

transferrin

Storage

Liver

Conjugated

bilirubin

Spleen

Intestine

Bilirubin

derivatives

Kidney

Amino

acids

Erythropoiesis

Red blood cells

120 days in

general circulation

Bile

ProcessFigure 19.6

Hemoglobin Breakdown

Hemoglobin isbroken down in macrophages, and the breakdown products are used or excreted.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Chapter 19 Cardiovascular System: Blood 649

circulation for about 10–12 hours and then move into other tis-

sues,where they become motile and seek out and phagocytize bac-

teria, antigen–antibody complexes (antigens and antibodies

bound together),and other foreign matter.Neutrophils also secrete

a class of enzymes called lysozymes (lı¯⬘so¯-zı¯mz),which are capa-

ble of destroying certain bacteria. Neutrophils usually survive for

1–2 days after leaving the circulation.

Eosinophils

Eosinophils (see table 19.2) contain cytoplasmic granules that

stain bright red with eosin, an acidic stain. They are motile cells

that leave the circulation to enter the tissues during an inﬂamma-

tory reaction.They are most common in tissues undergoing an al-

lergic response, and their numbers are elevated in the blood of

people with allergies.Eosinophils apparently reduce the inﬂamma-

tory response by producing enzymes that destroy inﬂammatory

chemicals like histamine.Eosinophils also release toxic chemicals

that attack certain worm parasites,such as tapeworms, ﬂukes, pin-

worms,and hookworms.

Basophils

Basophils (see table 19.2), the least common of all white blood

cells,contain large cytoplasmic granules that stain blue or purple

with basic dyes.Basophils, like eosinophils and neutrophils, leave

the circulation and migrate through the tissues,where they play a

role in both allergic and inﬂammatory reactions.Basophils contain

large amounts of histamine, which they release within tissues to

increase inﬂammation.They also release heparin, which inhibits

blood clotting.

Lymphocytes

The smallest white blood cells are lymphocytes,most of which are

slightly larger in diameter than red blood cells (see table 19.2).The

lymphocytic cytoplasm consists of only a thin, sometimes imper-

ceptible ring around the nucleus.Although lymphocytes originate

in red bone marrow,they migrate through the blood to lymphatic

tissues,where they can proliferate and produce more lymphocytes.

The majority of the body’s total lymphocyte population is in the

lymphatic tissues:the lymph nodes, spleen, tonsils, lymphatic nod-

ules,and thymus.

Although they cannot be identiﬁed by standard microscopic

examination,a number of different kinds of lymphocytes play im-

portant roles in immunity (see chapter 22 for details).For exam-

ple,B cells can be stimulated by bacteria or toxins to divide and

form cells that produce proteins called antibodies. Antibodies

can attach to bacteria and activate mechanisms that result in de-

struction of the bacteria.T cells protect against viruses and other

intracellular microorganisms by attacking and destroying the cells

in which they are found.In addition, T cells are involved in the de-

struction oftumor cells and tissue g raft rejections.

Monocytes

Monocytes are typically the largest ofthe white blood cells (see

table 19.2). They normally remain in the circulation for about 3

days,leave the circulation, become transformed into macrophages,

and migrate through various tissues. They phagocytize bacteria,

dead cells,cell fragments, and other debris within the tissues. An

increase in the number of monocytes is often associated with

chronic infections. In addition, macrophages can break down

phagocytized foreign substances and present the processed sub-

stances to lymphocytes,which results in activation of the lympho-

cytes (see chapter 22).

11. What are the two major functions of white blood cells?

Deﬁne ameboid movement, diapedesis, and chemotaxis.

12. Describe the morphology of the ﬁve types of white blood

cells.

13. Name the two white blood cellsthat function primarily as

phagocyticcells. Deﬁne lysozymes.

14. Which white blood cell reduces the inﬂammatory response?

Which white blood cell releaseshistamine and promotes

inﬂammation?

15. B and T cells are examples of what type of white blood cell?

Howdo these cells protect us against bacteria and viruses?

PREDICT

Based on their morphology, identifyeach of the white blood cells

shown in ﬁgure 19.8.

Platelets

Platelets, or thrombocytes(see ﬁgure 19.7 and table 19.2), are

minute fragments of cells consisting of a small amount of cyto-

plasm surrounded by a plasma membrane. Platelets are roughly

disk-shaped and average about 3 ␮m in diameter.The surface of

platelets has glycoproteins and proteins that allow platelets to at-

tach to other molecules,for example, collagen in connective tissue.

Figure 19.7

Standard Blood Smear

The red blood cellsare pink with whitish centers. The centersappear whitish

because lightmore readily shines through the thin center of the diskthan

through the thicker edges. The white blood cellshave been stained and have

pink-colored cytoplasm and purple-colored nuclei.

Platelet Red blood cells

Lymphocyte Neutrophil

White blood cells

LM 500x

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Some ofthese surface molecules, as well as molecules released from

granules in the platelet cytoplasm,play important roles in control-

ling blood loss. The platelet cytoplasm also contains actin and

myosin,which can cause contraction of the platelet (see section on

“Clot Retraction and Dissolution”on p.654).

The life expectancy of platelets is about 5–9 days.They are

produced within the red marrow and are derived from megakary-

ocytes (meg-a˘-kar⬘e¯-o¯-sı¯tz),which are extremely large cells with

diameters up to 100 ␮m.Small fragments of these cells break off

and enter the circulation as platelets.

Platelets play an important role in preventing blood loss by

(1) forming platelet plugs,which seal holes in small vessels, and (2)

by promoting the formation and contraction of clots,which help

seal offlarger wounds in the vessels.

16. What is a platelet? How are platelets formed?

17. What are the two major roles of platelets in preventing

blood loss?

Hemostasis

Objectives

■ Describe the stagesof hemostasis and clotting.

■ Give examplesof anticoagulants in the blood, and explain

theirimportance.

■ Describe the processesof clot retraction and dissolution.

Hemostasis (he¯⬘mo¯-sta¯-sis, he¯-mos⬘ ta˘-sis), the arrest of

bleeding,is very impor tant to the maintenance of homeostasis.If

not stopped,excessive bleeding from a cut or torn blood vessel can

result in a positive-feedback cycle, consisting of ever-decreasing

blood volume and blood pressure,leading away from homeostasis,

and resulting in death. Fortunately,when a blood vessel is dam-

aged,a number of events occur that help prevent excessive blood

loss.Vascular spasm, platelet plug formation, and coagulation can

cause hemostasis.

Vascular Spasm

Vascular spasmis an immediate but temporary closure of a blood

vessel resulting from contraction of smooth muscle within the

wall of the vessel. This constriction can close small vessels com-

pletely and stop the ﬂow ofblood through them. Nervous system

Part4 Regulationsand Maintenance650

reflexes and chemicals produce vascular spasms.For example,

during the formation of a platelet plug, platelets release throm-

boxanes (throm⬘bok-za¯nz), which are derived from certain

prostaglandins,and endothelial cells release the peptide endothe-

lin(en-do¯⬘the¯-lin).

PlateletPlug Formation

A platelet plug is an accumulation of platelets that can seal up

small breaks in blood vessels.Platelet plug formation is very im-

portant in maintaining the integrity of the circulatory system be-

cause small tears occur in the smaller vessels and capillaries many

times each day,and platelet plug formation quickly closes them.

People who lack the normal number of platelets tend to develop

numerous small hemorrhages in their skin and internal organs.

The formation of a platelet plug can be described as a series

of steps, but in actuality many of the steps take place simultane-

ously (ﬁgure 19.9).

1. Platelet adhesion occurs when platelets bind to collagen

exposed by blood vessel damage.Most platelet adhesion is

mediated through von Willebrand factor (VWF),which is

a protein produced and secreted by blood vessel endothelial

cells.Von Willebrand factor forms a bridge between colla-

gen and platelets by binding to platelet surface receptors

and collagen.In addition, other platelet surface receptors

can bind directly to collagen.

2. After platelets adhere to collagen, they become activated,

and in the platelet release reaction,adenosine diphosphate

(ADP),thromboxanes, and other chemicals are extruded

from the platelets by exocytosis.The ADP and thrombox-

anes stimulate other platelets to become activated and

release additional chemicals,thereby producing a cascade of

chemical release by the platelets.Thus, more and more

platelets become activated.

3. As platelets become activated, they express surface receptors

that can bind to ﬁbrinogen,a plasma protein. In platelet

aggregation,ﬁbr inogen forms a bridge between the surface

receptors ofdifferent platelets, resulting in the formation of

a platelet plug.

4. Activated platelets express phospholipids (platelet factor III)

and coagulation factor V,which are important in clot

formation (see following section on “Coagulation”).

LM 1200x

Figure 19.8

Identiﬁcation ofLeukocytes

See Predictquestion 4.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Chapter 19 Cardiovascular System: Blood 651

How Aspirin Increasesthe Risk of Bleeding

Thromboxanes, which activate platelets, are derived from certain

prostaglandins. Aspirin inhibitsprostaglandin synthesis and, therefore,

thromboxane synthesis, which resultsin reduced plateletactivation. If an

expectantmother ingests aspirin near the end of pregnancy,

prostaglandin synthesisis inhibited and several effects are possible. Two

ofthese effects are (1) the mother can experience excessive postpartum

hemorrhage because ofdecreased platelet function, and (2) the babycan

exhibitnumerous localized hemorrhages called petechiae(pe-te¯⬘ke¯-e¯)

over the surface ofits body as a result of decreased plateletfunction. If

the quantityof ingested aspirin is large, the infant, mother, or both may

die asa result of hemorrhage. On the other hand, in a stroke or heart

attack, plateletplugs and clots can form in vesselsand threaten the life of

the individual. Studiesof individuals who are at riskbecause of the

developmentof clots, such as people who have had a previous heart

attack, indicate thattaking smallamounts of aspirin daily can reduce the

likelihood ofclot formation and another heart attack. It’s notcurrently

recommended, however, thateveryone should take aspirin daily.

Coagulation

Vascular spasms and platelet plugs alone are not sufﬁcient to close

large tears or cuts.When a blood vessel is severely damaged, coagu-

lation(ko¯-ag-u¯-la¯⬘shu˘ n),or bloo d clotting, results in the formation

ofa clot. A blood clot is a network of threadlike protein ﬁbers, called

ﬁbrin,that traps blood cells, platelets, and ﬂuid (ﬁgure 19.10).

The formation of a blood clot depends on a number of pro-

teins, called coagulation factors, found within plasma (table

19.3).Normally the coagulation factors are in an inactive state and

don’t cause clotting.After injury, the clotting factors are activated

to produce a clot.This activation is a complex process involving

many chemical reactions, some of which require calcium ions

(Ca

2⫹

) and molecules on the surface ofactivated platelets, such as

phospholipids and coagulation factor V.

PREDICT

Whyis it advantageous for clot formation to involve molecules on the

surface ofactivated platelets?

The activation of clotting proteins occurs in three main

stages (ﬁgure 19.11). Stage 1 consists of the formation of pro-

thrombinase, stage 2 is the conversion of prothrombin to

thrombinby prothrombinase, and stage 3 consists of the conver-

sion of soluble ﬁbrinogen to insoluble ﬁbrin by thrombin.

von Willebrand factor

1. Platelet adhesion occurs when

von Willebrand factor connects

collagen and platelets.

2. The platelet release reaction is the

release of ADP, thromboxanes, and

other chemicals that activate other

platelets.

3. Platelet aggregation occurs when

fibrinogen receptors on activated

platelets bind to fibrinogen, connecting

the platelets to one another. A platelet

plug is formed by the accumulating

mass of platelets.

Platelet

plug

Smooth

muscle

cell

Blood

vessel

wall

Collagen

Endothelial

cell

Platelet

Granules

Fibrinogen

receptor

Fibrinogen

ADP

Thromboxane

ProcessFigure 19.9

PlateletPlug Formation

SEM 1400x

Figure 19.10

Blood Clot

A blood clotconsists of ﬁbrin ﬁbersthat trap red blood cells, platelets, and ﬂuid.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Depending on how prothrombinase is formed in stage 1,two sep-

arate pathways for coagulation can occur: the extrinsic clotting

pathwayand the intrinsic clotting pathway.

ExtrinsicClotting Pathway

The extrinsic clotting pathway is so named because it begins with

chemicals that are outside of,or extrinsic to, the blood (see ﬁgure

19.11).In stage 1, damaged tissues release a mixture of lipoproteins

and phospholipids called thromboplastin (throm-bo¯-plas⬘tin),

also known as tissue factor (TF),or factor III. Thromboplastin, in

the presence ofCa

2⫹

,forms a complex with factor VII, which acti-

vates factor X.On the surface of platelets, activated factor X, factor

V,platelet phospholipids, and Ca

2⫹

complex to form prothrombi-

nase.In stage 2, prothrombinase converts the soluble plasma pro-

tein prothrombin into the enzyme thrombin. During stage 3,

thrombin converts the soluble plasma protein ﬁbrinogen into the

insoluble protein ﬁbrin. Fibrin forms the ﬁbrous network of the

clot.Thrombin also stimulates factor XIII activation, which is nec-

essary to stabilize the clot.

Part4 Regulationsand Maintenance652

IntrinsicClotting Pathway

The intrinsic clotting pathway is so named because it begins with

chemicals that are inside,or intrinsic to, the blood (see ﬁgure 19.11).

In stage 1,damage to blood vessels can expose collagen in the con-

nective tissue beneath the epithelium lining the blood vessel.When

plasma factor XII comes into contact with collagen,factor XII is ac-

tivated and it stimulates factor XI,which in turn activates factor IX.

Activated factor IX joins with factor VIII,platelet phospholipids,and

2⫹

to activate factor X.On the surface of platelets, activated factor

X,factor V, platelet phospholipids,and Ca

2⫹

complex to form pro-

thrombinase.Stages 2 and 3 then are activated, and a clot results.

Although once considered distinct pathways,it’s now known

that the extrinsic pathway can activate the clotting proteins in the

intrinsic pathway.The TF–VII complex from the extrinsic pathway

can stimulate the formation ofactivated factors IX in the intrinsic

pathway.When tissues are damaged, thromboplastin also rapidly

leads to the production of thrombin,which can activate many of

the clotting proteins such as factor XI and prothrombinase.Thus,

thrombin is part of a positive-feedback system in which thrombin

production stimulates the production of additional thrombin.

Table 19.3

Factor Number Name (synonym) Description and Function

Coagulation Factors

I Fibrinogen Plasma protein synthesized in liver; converted to fibrin in stage 3

II Prothrombin Plasma protein synthesized in liver (requires vitamin K); converted to thrombin

in stage 2

III Thromboplastin (tissue factor) Mixture of lipoproteins released from damaged tissue; required in extrinsic

stage 1

IV Calcium ion Required throughout entire clotting sequence

V Proaccelerin (labile factor) Plasma protein synthesized in liver; activated form functions in stages 1 and 2

of both intrinsic and extrinsic clotting pathways

VI Once thought to be involved but no longer accepted as playing a role in

coagulation; apparently the same as activated factor V

VII Serum prothrombin conversion Plasma protein synthesized in liver (requires vitamin K); functions in extrinsic

accelerator (stable factor, proconvertin) stage 1

VIII Antihemophilic factor (antihemophilic Plasma protein synthesized in megakaryocytes and endothelial cells; required

globulin) for intrinsic stage 1

IX Plasma thromboplastin component Plasma protein synthesized in liver (requires vitamin K); required for intrinsic

(Christmas factor) stage 1

X Stuart factor (Stuart-Prower factor) Plasma protein synthesized in liver (requires vitamin K); required in stages 1

and 2 of both intrinsic and extrinsic clotting pathways

XI Plasma thromboplastin antecedent Plasma protein synthesized in liver; required for intrinsic stage 1

XII Hageman factor Plasma protein required for intrinsic stage 1

XIII Fibrin-stabilizing factor Protein found in plasma and platelets; required for stage 3

Platelet Factors

I Platelet accelerator Same as plasma factor V

II Thrombin accelerator Accelerates thrombin (intrinsic clotting pathway) and fibrin production

III Phospholipids necessary for the intrinsic and extrinsic clotting pathways

IV Binds heparin, which prevents clot formation

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Chapter 19 Cardiovascular System: Blood 653

Thrombin also has a positive-feedback effect on coagulation by

stimulating platelet activation.

18. What is a vascular spasm? Name two factors that produce

it. Whatis the source of thromboxanes and endothelin?

19. What is the function of a platelet plug? Describe the process

of plateletplug formation. How are platelets an important

partof clot formation?

20. What is a clot and what is its function?

21. What are coagulation factors?

22. Clotting is divided into three stages. Describe the ﬁnal

eventthat occurs in each stage.

23. What is the difference between extrinsic and intrinsic

activation of clotting?

ProcessFigure 19.11

ClotFormation

Tissue

damage

Contact with

damaged blood vessel

Activated

factor XII

Tissue

factor (TF)

Stage 1: Damage to tissue or

blood vessels activates clotting

factors that activate other clotting

factors, which leads to the

production of prothrombinase.

The activated factors are within

white ovals

, whereas the

inactive precursors are shown

yellow ovals

Stage 2: Prothrombin is activated

by prothrombinase to form

thrombin.

Stage 3: Fibrinogen is activated

by thrombin to form fibrin, which

forms the clot.

Stage 1 can be activated in two ways:

Intrinsic clotting pathway starts

when inactive factor XII, which is in

the plasma, is activated by coming

into contact with a damaged blood

vessel.

Extrinsic clotting pathway starts

with tissue factor, which is released

outside of the plasma in damaged

tissue.

Factor VII

TF/factor VII

complex

Factor XII

Activated

factor XI

Factor XI

Activated

factor IX

Factor IX

Activated

factor X

Prothrombinase

Thrombin

Fibrin

Fibrinogen

Prothrombin

Fibrin

clot

Factor X

Activated

factor XIII

Factor XIII

Factor VIII

platelet phospholipids, Ca

Factor V, platelet

phospholipids, Ca

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

How Vitamin KHelps to Prevent Bleeding

Manyof the factors involved in clot formation require vitamin Kfor their

production (see table 19.3). Humansrely on two sourcesfor vitamin K.

Abouthalf comes from the diet, and half comesfrom bacteria within the

large intestine. Antibioticstaken to ﬁght bacterial infectionssometimes

killthese intestinal bacteria, thereby reducing vitamin Klevels and

resulting in bleeding problems. Vitamin Ksupplements maybe necessary

for patientson prolonged antibiotic therapy. Newbornslack these

intestinalbacteria, and a vitamin K injection is routinely given to infantsat

birth. Infantscan also obtain vitamin K from food such asmilk. Because

cow’smilk containsmore vitamin K than does human milk, breast-fed

infantsare more susceptible to hemorrhage than bottle-fed infants.

The absorption ofvitamin K, which is a fat-soluble vitamin, from

the intestine requiresthe presence of bile. Disorders like obstruction of

bile ﬂow to the intestine can interfere with vitamin Kabsorption and lead

to insufﬁcientclotting. Liver diseases that result in the decreased

synthesisof clotting factors can also lead to insufﬁcientclot formation.

Controlof Clot Formation

Without control,coagulation would spread from the point of initi-

ation to the entire circulatory system. Furthermore, vessels in a

healthy person contain rough areas that can stimulate clot forma-

tion,and small amounts of prothrombin are constantly being con-

verted into thrombin. To prevent unwanted clotting,the blood

contains several anticoagulants(an⬘te¯-ko¯-ag⬘u¯-lantz), which pre-

vent coagulation factors from initiating clot formation.Only when

coagulation factor concentrations exceed a given threshold does

coagulation occur.At the site ofinjur y,so many coagulation factors

are activated that the anticoagulants are unable to prevent clot for-

mation.Away from the injury site, however,the activated coagula-

tion factors are diluted in the blood, anticoagulants neutralize

them,and clotting is prevented.

Examples of anticoagulants in the blood are antithrombin,

heparin, and prostacyclin.Antithrombin, a plasma protein pro-

duced by the liver,slowly inactivates thrombin.Heparin, produced

by basophils and endothelial cells,increases the effectiveness of an-

tithrombin because heparin and antithrombin together rapidly

inactivate thrombin. Prostacyclin (pros-ta˘-sı¯⬘klin) is a pro-

staglandin derivative produced by endothelial cells.It counteracts

the effects of thrombin by causing vasodilation and by inhibiting

the release ofcoagulation factors from platelets.

Anticoagulants are also important when blood is outside

the body.They prevent the clotting of blood used in transfusions

and laboratory blood tests. Examples include heparin,

ethylenediaminetetraacetic (eth⬘il-e¯n-dı¯⬘a˘-me¯n-tet-ra˘-a˘-se¯⬘tik)

acid (EDTA),and sodium citrate. EDTA and sodium citrate pre-

vent clot formation by binding to Ca

2⫹

,thus making the ions inac-

cessible for clotting reactions.

Part4 Regulationsand Maintenance654

The Danger ofUnwanted Clots

When plateletsencounter damaged or diseased areason the walls of

blood vesselsor the heart, an attached clot called a thrombus

(throm⬘bu˘s) may form. A thrombus that breaks loose and begins to ﬂoat

through the circulation iscalled an embolus (em⬘bo¯-lu˘s). Both thrombi

and emboli can resultin death if they blockvessels that supply blood to

essentialorgans, such as the heart, brain, or lungs. Abnormal

coagulation can be prevented or hindered bythe injection of

anticoagulantslike heparin, which acts rapidly. Coumadin (koo⬘ma˘-din),

or warfarin (war⬘fa˘-rin), acts more slowly than heparin. Coumadin

preventsclot formation by suppressing the production of vitamin

K–dependentcoagulation factors (II, VII, IX, and X) by the liver.

Interestingly, coumadin wasﬁrst used as a rat poison bycausing rats to

bleed to death. In smalldoses, warfarin is a proven, effective

anticoagulantin humans. Caution is necessarywith anticoagulant

treatment, however, because the patientcan hemorrhage internallyor

bleed excessivelywhen cut.

ClotRetraction and Dissolution

The ﬁbrin meshwork constituting the clot adheres to the walls ofthe

blood vessel.Once a clot has formed, it begins to condense into a

denser,compact structure through a process known as clot retrac-

tion. Platelets contain the contractile proteins actin and myosin,

which operate in a similar fashion to that of actin and myosin in

smooth muscle (see chapter 9).Platelets form small extensions that

attach to ﬁbrin.Contraction of the extensions pulls on the ﬁbrin and

is responsible for clot retraction.As the clot condenses, a ﬂuid called

serum (se¯r⬘u˘m) is squeezed out of it. Serum is plasma from which

ﬁbrinogen and some ofthe clotting factors have been removed.

Consolidation of the clot pulls the edges of the damaged

blood vessel together,which can help to stop the ﬂow of blood, re-

duce infection, and enhance healing. The damaged vessel is re-

paired by the movement ofﬁbroblasts into the damaged area and

the formation ofnew connective tissue. In addition, epithelial cells

around the wound proliferate and ﬁll in the torn area.

The clot usually is dissolved within a few days after clot for-

mation by a process called ﬁbrinolysis(f ı¯-bri-nol⬘i-sis),which in-

volves the activity of plasmin (plaz⬘min), an enzyme that

hydrolyzes ﬁbrin.Plasmin is for med from inactive plasminogen,

which is a normal blood protein.It’s activated by thrombin,factor

XII,tissue plasminogen activator (t-PA), urokinase,and lysosomal

enzymes released from damaged tissues (ﬁgure 19.12).In disorders

that are caused by blockage ofa vessel by a clot, such as a heart at-

tack,dissolving the clot can restore blood ﬂow and reduce damage

to tissues.For example, streptokinase (a bacterial enzyme),t-PA, or

urokinase can be injected into the blood or introduced at the clot

site by means ofa catheter. These substances convert plasminogen

to plasmin,which breaks down the clot.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Chapter 19 Cardiovascular System: Blood 655

24. What is the function of anticoagulants in blood? Name three

anticoagulantsin blood, and explain how they prevent clot

formation.

25. Deﬁne the terms thrombus and embolus, and explain why

theyare dangerous.

26. Describe clot retraction. What is serum?

27. What is ﬁbrinolysis? How does it occur?

Blood Grouping

Objective

■ Explain the basisof ABO and Rh incompatibilities.

Iflarge quantities of blood are lost during surger y or in an ac-

cident,the patient can go into shock and die unless a transfusion or

infusion is performed.A transfusion is the transfer of blood or blood

components from one individual to another.When large quantities

ofblood are lost, red blood cells must be replaced so that the oxygen-

carrying capacity of the blood is restored.An infusion is the intro-

duction of a ﬂuid other than blood, such as a saline or glucose

solution,into the blood. In many cases, the return of blood volume

to normal levels is all that is necessary to prevent shock.Eventually,

the body produces red blood cells to replace those that were lost.

Early attempts to transfuse blood from one person to an-

other were often unsuccessful because they resulted in transfusion

reactions, which included clotting within blood vessels, kidney

damage,and death. It’s now known that transfusion reactions are

caused by interactions between antigens and antibodies (see chap-

ter 22). In brief, the surfaces of red blood cells have molecules

called antigens (an⬘ti-jenz), and, in the plasma, molecules called

antibodies are present.Antibodies are very speciﬁc, meaning that

each antibody can combine only with a certain antigen.When the

antibodies in the plasma bind to the antigens on the surfaces ofthe

red blood cells,they form molecular bridges that connect the red

blood cells. As a result, agglutination (a˘-gloo-ti-na¯⬘shu˘n), or

clumping, of the cells occurs.The combination of the antibodies

with the antigens can also initiate reactions that cause hemolysis,

or rupture of the red blood cells. Because the antigen–antibody

combinations can cause agglutination,the antigens are often called

agglutinogens (a˘-gloo-tin⬘o¯-jenz), and the antibodies are called

agglutinins(a˘-gloo⬘ti-ninz).

The antigens on the surface ofred blood cells have been cat-

egorized into bloodgroups, and more than 35 blood groups, most

of which are rare,have been identiﬁed. For transfusions, the ABO

and Rh blood groups are among the most important.Other well-

known groups include the Lewis, Duffy,MNSs, Kidd, Kell, and

Lutheran groups.

ABO Blood Group

In theABO blood g roup, type A blood has type A antigens, type

B blood has type B antigens, type AB blood has both types of

antigens,and t ype O blood has neither A nor B antigens on the

surface ofred blood cells (ﬁgure 19.13). In addition, plasma from

type A blood contains anti-B antibodies,which act against type B

antigens,whereas plasma from type B blood contains anti-A an-

tibodies, which act against type A antigens. Type AB blood has

neither type of antibody,and ty pe O blood has both anti-A and

anti-B antibodies.

The ABO blood types are not found in equal numbers. In

Caucasians in the United States,the distribution is ty pe O,47%;

type A, 41%; type B, 9%; and type AB, 3%. Among African-

Americans, the distribution is type O,46%; type A, 27%; type B,

20%;and type AB, 7%.

Antibodies normally don’t develop against an antigen unless

the body is exposed to that antigen.This means, for example, that

a person with type A blood should not have anti-B antibodies un-

less he or she has received a transfusion of type B blood, which

contains type B antigens.People with type A blood do have anti-B

antibodies,however, even though they have never received a trans-

fusion of type B blood. One possible explanation is that type A or

B antigens on bacteria or food in the digestive tract stimulate the

formation of antibodies against antigens that are different from

one’s own antigens.Thus a person with type A blood would pro-

duce anti-B antibodies against the B antigens on the bacteria or

food.In support of this hypothesis is the observation that anti-A

and anti-B antibodies are not found in the blood until about 2

months after birth.

A blood donor gives blood, and a recipient receives blood.

Usually a donor can give blood to a recipient ifthey both have the

same blood type. For example,a person with ty pe A blood could

donate to another person with type A blood.No ABO transfusion

reaction would occur because the recipient has no anti-A antibod-

ies against the type A antigen.On the other hand, if ty pe A blood

were donated to a person with type B blood,a transfusion reaction

would occur because the person with type B blood has anti-A anti-

bodies against the type A antigen,and agg lutination would result

(ﬁgure 19.14).

Historically,people with type O blood have been called uni-

versal donors because they usually can give blood to the other ABO

blood types without causing an ABO transfusion reaction.Their red

blood cells have no ABO surface antigens and,therefore,do not react

Plasmin

Clot

dissolution

Fibrin

Plasminogen

Thrombin,

factor XII, t-PA, urokinase,

lysosomal enzymes

Figure 19.12

Fibrinolysis

Plasminogen isconverted by thrombin, factor XII, tissue plasminogen

activator (t-PA), urokinase, or lysosomalenzymesto the active enzyme

plasmin. Plasmin breaksthe ﬁbrin molecules and therefore the clot into

smaller pieces, which are washed awayin the blood or are phagocytized.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Part4 Regulationsand Maintenance656

Figure 19.14

Agglutination Reaction

Type A

Red blood cells with type A

surface antigens and plasma

with anti-B antibodies

Type B

Red blood cells with type B

surface antigens and plasma

with anti-A antibodies

Type AB

Red blood cells with both

type A and type B surface

antigens, and neither anti-A

nor anti-B plasma antibodies

Type O

Red blood cells with neither

type A nor type B surface

antigens, but both anti-A and

anti-B plasma antibodies

Red blood

cells

Plasma

Antigen A Antigen B Antigens A and B Neither antigen

A nor B

Anti-B antibody Anti-A antibody Anti-A and Anti-B

antibodies

Neither Anti-A nor

Anti-B antibodies

Figure 19.13

ABO Blood Groups

Anti-A antibody

in type B blood

of recipient

Type A blood of donor

Anti-B antibody

in type A blood

of recipient

Type A blood of donor

(a) No agglutination

reaction. Type A blood

donated to a type A

recipient does not

cause an agglutination

reaction because the

anti-B antibodies in the

recipient do not

combine with the type

A antigens on the red

blood cells in the

donated blood.

(b) Agglutination

reaction. Type A blood

donated to a type B

recipient causes an

agglutination reaction

because the anti-A

antibodies in the

recipient combine with

the type A antigens on

the red blood cells in the

donated blood.

Antigen and

antibody do

not match

Antigen and

antibody

match

Agglutination

No agglutination

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Chapter 19 Cardiovascular System: Blood 657

with the recipient’s anti-A or anti-B antibodies.For example, if type

O blood is given to a person with type A blood,the type O red blood

cells do not react with the anti-B antibodies in the recipient’s blood.

In a similar fashion,if type O blood is given to a person with type B

blood,no reaction occurs to the recipient’s anti-A antibodies.

The term universal donor is misleading, however.Transfu-

sion of type O blood, in some cases, produces a transfusion reac-

tion for two reasons. First, other blood groups can cause a

transfusion reaction.Second, antibodies in the blood of the donor

can react with antigens in the blood of the recipient.For example,

type O blood has anti-A and anti-B antibodies.If t ype O blood is

transfused into a person with type A blood,the anti-A antibodies

(in the type O blood) react against the A antigens (in the type A

blood).Usually such reactions are not serious because the antibod-

ies in the donor’s blood are diluted in the blood ofthe recipient,

and few reactions take place. Because type O blood sometimes

causes transfusion reactions, it’s given to a person with another

blood type only in life-or-death emergency situations.

28. What are blood groups, and how do they cause

transfusion reactions? Deﬁne the termsagglutination and

hemolysis.

29. What kinds of antigens and antibodies are found in each of

the fourABO blood types?

30. Why is a person with type O blood considered to be a

universal donor?

PREDICT

Historically, people with type AB blood were called universal

recipients. Whatis the rationale for this term? Explain whythe term is

misleading.

Rh Blood Group

Another important blood group is the Rh blood group,so named

because it was ﬁrst studied in rhesus monkeys. People are Rh-

positive if they have certain Rh antigens (the D antigens) on the

surface oftheir red blood cells, and people are Rh-negative if they

do not have these Rh antigens.About 85% of Caucasians in the

United States and 88% ofAfrican-Americans are Rh-positive. The

ABO blood type and the Rh blood type usually are designated to-

gether.For example, a person designated as A positive is type A in

the ABO blood group and Rh-positive.The rarest combination in

the United States is AB negative,which occurs in less than 1% of all

Americans.

Antibodies against the Rh antigen do not develop unless an

Rh-negative person is exposed to Rh-positive blood.This can oc-

cur through a transfusion or by transfer ofblood between a mother

and her fetus across the placenta.When an Rh-negative person re-

ceives a transfusion of Rh-positive blood, the recipient becomes

sensitized to the Rh antigen and produces anti-Rh antibodies.If

the Rh-negative person is unfortunate enough to receive a second

transfusion of Rh-positive blood after becoming sensitized, a

transfusion reaction results.

Rh incompatibility can pose a major problem in some

pregnancies when the mother is Rh-negative and the fetus is Rh-

positive (ﬁgure 19.15).If fetal blood leaks through the placenta

and mixes with the mother’s blood,the mother becomes sensi-

tized to the Rh antigen.The mother produces anti-Rh antibodies

that cross the placenta and cause agglutination and hemolysis of

fetal red blood cells.This disorder is called hemolytic disease of

the newborn (HDN), or er ythroblastosis fetalis (e˘-rith⬘ro¯-

blas-to¯⬘sis f e¯-ta⬘lis), and it may be fatal to the fetus. In the

woman’s ﬁrst pregnancy,however, usually no problem occurs.

The leakage offetal blood is usually the result of a tear in the pla-

centa that takes place either late in the pregnancy or during deliv-

ery. Thus, not enough time exists for the mother to produce

enough anti-Rh antibodies to harm the fetus. In later pregnan-

cies,however,a problem can arise because the mother has already

been sensitized to the Rh antigen. Consequently,if the fetus is

Rh-positive and if any leakage of fetal blood into the mother’s

blood occurs,she rapidly produces large amounts of anti-Rh an-

tibodies,and HDN develops.

HDN can be prevented ifthe Rh-negative woman is given an

injection of a speciﬁc type of antibody preparation, called Rh

(D)

immune globulin (RhoGAM).The injection can be administered

during the pregnancy or before or immediately after each delivery

or abortion.The injection contains antibodies against Rh antigens.

The injected antibodies bind to the Rh antigens of any fetal red

blood cells that may have entered the mother’s blood.This treat-

ment inactivates the fetal Rh antigens and prevents sensitization of

the mother.

IfHDN develops, treatment consists of slowly removing the

newborn’s blood and replacing it with Rh-negative blood.The

newborn can also be exposed to ﬂuorescent light,because the light

helps to break down the large amounts ofbilirubin formed as a re-

sult ofred blood cell destruction. High levels of bilirubin are toxic

to the nervous system and can damage brain tissue.

31. What is meant by the term Rh-positive?

32. What Rh blood types must the mother and fetus have before

HDN can occur?

33. How is HDN harmful to the fetus?

34. Why doesn’t HDN usually develop in the ﬁrst pregnancy?

35. How can HDN be prevented? How is HDN treated?

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Diagnostic Blood Tests

Objective

■ Describe diagnosticblood tests and the normal values for

the tests. Give examplesof disorders that produce

abnormal testresults.

Type and Crossmatch

To prevent transfusion reactions the blood is typed,and a cross-

matchis made. Blood typing determines the ABO and Rh blood

groups ofthe blood sample. Typically, the cells are separated from

the serum.The cells are tested with known antibodies to determine

the type of antigen on the cell surface. For example,if a patient’s

blood cells agglutinate when mixed with anti-A antibodies but do

not agglutinate when mixed with anti-B antibodies,it’s concluded

that the cells have type A antigen.In a similar fashion, the serum is

mixed with known cell types (antigens) to determine the type of

antibodies in the serum.

Part4 Regulationsand Maintenance658

Normally,donor blood must match the ABO and Rh type of

the recipient.Because other blood groups can also cause a transfu-

sion reaction, however,a crossmatch is performed. In a cross-

match, the donor’s blood cells are mixed with the recipient’s

serum, and the donor’s serum is mixed with the recipient’s cells.

The donor’s blood is considered safe for transfusion only ifno ag-

glutination occurs in either match.

Complete Blood Count

Thecomplete blood count (CBC) is an analysis of the blood that

provides much information.It consists of a red blood count, he-

moglobin and hematocrit measurements,a white blood count, and

a differential white blood count.

Red Blood Count

Blood cell counts usually are done automatically with an electronic

instrument,but they can also be done manually with a microscope.

The normal range for a red blood count (RBC) is the number

Maternal

circulation

Maternal

Rh-negative

red blood cell

Anti-Rh

antibodies

2. The mother is sensitized to the Rh

antigen and produces anti-Rh

antibodies. Because this usually

happens after delivery, there is no

effect on the fetus in the first

pregnancy.

Agglutination of

fetal Rh-positive

red blood cells

leads to HDN

Maternal

circulation

Maternal anti-Rh

antibodies cross

the placenta

3. During a subsequent pregnancy with an

Rh-positive fetus, Rh-positive red blood

cells cross the placenta, enter the maternal

circulation, and stimulate the mother to

produce antibodies against the Rh antigen.

Antibody production is rapid because the

mother has been sensitized to the Rh

antigen.

4. The anti-Rh antibodies from the mother

cross the placenta, causing agglutination

and hemolysis of fetal red blood cells, and

hemolytic disease of the newborn (HDN)

develops.

Fetal

Rh-positive

red blood cell

Maternal

circulation

Maternal

Rh-negative

red blood cell

Fetal Rh-positive

red blood cell enters

maternal circulation

1. Before or during delivery, Rh-positive

red blood cells from the fetus enter

the blood of an Rh-negative woman

through a tear in the placenta.

ProcessFigure 19.15

HemolyticDisease of the Newborn (HDN)

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Chapter 19 Cardiovascular System: Blood 659

(expressed in millions) ofred blood cells per microliter of blood. It

is 4.6–6.2 million/␮L of blood for a male,and 4.2–5.4 million/␮L

of blood for a female. Erythrocytosis (e˘-rith⬘ro¯-sı¯-to¯⬘sis) is an

overabundance of red blood cells. It can result from a decreased

oxygen supply,which stimulates ery thropoietin secretion by the

kidney,or from red bone marrow tumors. Because red blood cells

tend to stick to one another,increasing the number of red blood

cells makes it more difﬁcult for blood to ﬂow.Consequently,eryth-

rocytosis increases the workload of the heart. It also can reduce

blood ﬂow through tissues and,if severe, can result in plugging of

small blood vessels (capillaries).

Hemoglobin Measurement

The hemoglobin measurement determines the amount of hemo-

globin in a given volume ofblood, usually expressed as grams of he-

moglobin per 100 mL ofblood. The normal hemoglobin count for a

male is 14–18 g/100 mL ofblood, and for a female it is 12–16 g/100

mL ofblood. Abnormally low hemoglobin is an indication of anemia

(a˘-ne¯⬘me¯-a˘), which is a reduced number of red blood cells per 100 mL

ofblood or a reduced amount of hemoglobin in each red blood cell.

HematocritMeasurement

The percentage oftotal blood volume composed of red blood cells

is the hematocrit (he¯⬘ma˘-to¯-krit,hem⬘a˘-to¯ -krit).One way to de-

termine hematocrit is to place blood in a tube and spin the tube in

a centrifuge.The formed elements are heavier than the plasma and

are forced to one end ofthe tube (ﬁgure 19.16). White blood cells

and platelets form a thin,whitish layer, called the buffy coat, be-

tween the plasma and the red blood cells.The red blood cells ac-

count for 40%–54% of the total blood volume in males and

38%–47% in females.

The number and size ofred blood cells affect the hematocrit

measurement. Normocy tes (no¯r⬘mo¯-sı¯tz) are normal sized red

blood cells with a diameter of 7.5 ␮m. Microcytes (mı¯⬘kro¯-sı¯tz)

are smaller than normal with a diameter of 6 ␮m or less, and

macrocytes(mak⬘kro¯-sı¯tz) are larger than normal with a diameter

9 ␮m or greater. Blood disorders can result in abnormal hemat-

ocrit measurement because they cause red blood cells numbers to

be abnormally high or low,or cause red blood cells to be abnor-

mally small or large (see “Disorders ofthe Blood” on p. 660).A de-

creased hematocrit indicates that the volume of red blood cells is

less than normal.It can result from a decreased number of normo-

cytes or a normal number of microcytes.For example, inadequate

iron in the diet can impair hemoglobin production.Consequently,

during their formation red blood cells do not ﬁll with hemoglobin,

and they remain smaller than normal.

White Blood Count

Awhite bloo d count (WBC) measures the total number of white

blood cells in the blood.Normally 5000–10,000 white blood cells

are present in each microliter of blood. Leukopenia (loo-ko¯-

pe¯⬘ne¯-a˘) is a lower-than-normal WBC and can indicate depression

or destruction of the red marrow by radiation,dr ugs,tumor, or a

deﬁciency ofvitamin B

or folate.Leukocytosis (loo⬘ko¯-sı¯-to¯⬘sis)

is an abnormally high WBC.Leukemia (loo-ke¯⬘me¯-a˘) (a cancer of

the red marrow) often results in leukocytosis,but the white blood

cells have an abnormal structure and function.Bacterial infections

also can cause leukocytosis.

DifferentialWhite Blood Count

Adifferential white blood count determines the percentage of each

of the ﬁve kinds of white blood cells in the WBC. Normally neu-

trophils account for 60%–70%; lymphocytes, 20%–30%; mono-

cytes, 2%–8%; eosinophils, 1%–4%;and basophils, 0.5%–1%. A

differential WBC can provide much insight about a patient’s condi-

tion.For example,in patients w ith bacterial infections the neutrophil

count is often greatly increased,whereas in patients with allergic re-

actions the eosinophil and basophil counts are elevated.

Clotting

Two measurements that test the ability ofthe blood to clot are the

platelet count and prothrombin time.

PlateletCount

A normal platelet countis 250,000–400,000 platelets per microliter

of blood. Thrombocy topenia (throm⬘bo¯-sı¯-to¯-pe¯⬘ne¯-a˘) is a condi-

tion in which the platelet count is greatly reduced,resulting in chronic

bleeding through small vessels and capillaries.It can be caused by de-

creased platelet production as a result ofhereditary disorders, lack of

vitamin B

,drug therapy, or radiation therapy.

Figure 19.16

Hematocrit

Blood iswithdrawn into a capillary tube and placed in a centrifuge. The blood

isseparated into plasma, red blood cells, and a smallamount of white blood

cellsand platelets, which rest on the red blood cells. The hematocrit

measurementis the percent of the blood volume thatis red blood cells. It

doesn’tmeasure the white blood cells and platelets. Normal hematocritsfor a

male (a) and a female (b) are shown.

100

Hematocrit scale

Plasma

(a) (b)

White blood cells

and platelets form

the buffy coat

Red blood cells

Withdraw

blood into

hematocrit

tube

Centrifuge blood in

the hematocrit tube

Hematocrit tube

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Part4 Regulationsand Maintenance660

Clinical Focus Disordersof the Blood

Erythrocytosis

Erythrocytosis(e˘-rith⬘ro¯-sı¯-to¯⬘sis) isan over-

abundance ofred blood cells, resulting in in-

creased blood viscosity, reduced ﬂow rates,

and, if severe, plugging of the capillaries.

Relative erythrocytosis results from de-

creased plasma volume, such as that

caused by dehydration, diuretics, and

burns. Primary erythrocytosis, often called

polycythemia vera(pol⬘e¯-sı¯-the¯⬘me¯-a˘ ve⬘ra),

isa stem cell defect of unknown cause that

results in the overproduction of red blood

cells, granulocytes, and platelets. Erythro-

poietin levelsare low and the spleen can be

enlarged. Secondary erythrocytosis (poly-

cythemia)results from a decreased oxygen

supply, such asthat which occursat high al-

titudes, in chronic obstructive pulmonary

disease, or in congestive heartfailure. The

resulting decrease in oxygen deliveryto the

kidneysstimulates erythropoietin secretion

and causes an increase in red blood cell

production. In both types of polycythemia

the increased number ofred blood cells in-

creases blood viscosityand blood volume.

There can be clogging ofcapillaries and the

developmentof hypertension.

Anemia

Anemia(a˘-ne¯⬘me¯-a˘) isa deﬁciencyof hemo-

globin in the blood. Itcan result from a de-

crease in the number ofred blood cells, a

decrease in the amount ofhemoglobin in

each red blood cell, or both. The decreased

hemoglobin reducesthe ability of the blood

to transportoxygen. Anemic patients suffer

from a lackof energy and feel excessively

tired and listless. Theycan appear pale and

quickly become short ofbreath with only

slightexertion.

One general cause ofanemia is nutri-

tional deﬁciencies. Iron-deﬁciency anemia

resultsfrom a deﬁcient intake or absorption

of iron or from excessive iron loss. Conse-

quently, not enough hemoglobin is pro-

duced, and the red blood cellsare smaller

than normal (microcytic). Folate deﬁciency

can also cause anemia. An inadequate

amount of folate in the diet is the usual

cause offolate deﬁciency, with the disorder

developing mostoften in the poor, in preg-

nantwomen, and in chronic alcoholics. Be-

cause folate helpsin the synthesis of DNA,

folate deﬁciency resultsin fewer cell divi-

sions. There isdecreased red blood cell pro-

duction, but the cells grow larger than

normal (macrocytic). Another type of nutri-

tional anemia is pernicious (per-nish⬘u˘s)

anemia, which is caused by inadequate

amounts of vitamin B

. Because vitamin

isimportant for folate synthesis, inade-

quate amountsof it can also result in the de-

creased production of red blood cellsthat

are larger than normal. Although inadequate

levels of vitamin B

in the diet can cause

perniciousanemia, the usual cause is insuf-

ﬁcient absorption of the vitamin. Normally

the stomach producesintrinsic factor, a pro-

tein thatbinds to vitamin B

. The combined

molecules pass into the small intestine,

where intrinsicfactor facilitates the absorp-

tion ofthe vitamin. Without adequate levels

ofintrinsic factor, insufﬁcient vitamin B

absorbed, and perniciousanemia develops.

Presentevidence suggests that the inability

to produce intrinsicfactor is due to an auto-

immune disease in which the body’s im-

mune system damages the cells in the

stomach thatproduce intrinsic factor.

Another general cause of anemia is

lossor destruction of red blood cells. Hem-

orrhagic(hem-o˘-raj⬘ik)anemia results from

a loss of blood, such as can result from

trauma, ulcers, or excessive menstrual

bleeding. Chronicblood loss, in which small

amountsof blood are lost over time, can re-

sult in iron-deﬁciency anemia. Hemolytic

(he¯-mo¯-lit⬘ik)anemia is a disorder in which

red blood cellsrupture or are destroyed at

an excessive rate. Itcan be caused by inher-

ited defects within the red blood cells. For

example, one kind of inherited hemolytic

anemia resultsfrom a defect in the plasma

membrane that causes red blood cellsto

rupture easily. Manykinds of hemolytic ane-

mia resultfrom unusual damage to the red

blood cellsby drugs, snake venom, artiﬁcial

heart valves, autoimmune disease, or he-

molyticdisease of the newborn.

Aplasticanemia is caused by an inabil-

ityof the red bone marrow to produce nor-

mal red blood cells (normocytic). It’s

usually acquired as a result ofdamage to

the red marrow by chemicals (e.g., ben-

zene), drugs (e.g., certain antibiotics and

sedatives), or radiation.

Some anemiasresult from inadequate

or defective hemoglobin production.

Thalassemia(thal-a˘-se¯⬘me¯-a˘) isa hereditary

disease found predominantlyin people of

Mediterranean, Asian, and African ancestry.

It’scaused by insufﬁcient production of the

globin part of the hemoglobin molecule.

The major form of the disease results in

death byage 20, the minor form in a mild

anemia. Sickle-cell disease is a hereditary

disease found mostly in people of African

ancestrybut also occasionally among peo-

ple of Mediterranean heritage. Itresults in

the formation ofan abnormal hemoglobin,

in which the red blood cellsassume a rigid

sickle shape and plug up smallblood ves-

sels (ﬁgure A). They are also more fragile

than normal red blood cells. In itssevere

form, sickle-celldisease is usually fatal be-

fore the person is30 years of age, whereas

in itsminor form, sickle-cell trait, symptoms

usuallydo not occur.

Von Willebrand’sDisease

Von Willebrand’sdisease is the most com-

mon inherited bleeding disorder; it occurs

asfrequently as 1 in 1000 individuals. Von

Willebrand factor (vWF) helps platelets to

stickto collagen (platelet adhesion) and is

the plasma carrier for factor VIII (see

discussion on “Coagulation” on p. 651

and table 19.3). One treatment for von

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Chapter 19 Cardiovascular System: Blood 661

Willebrand’sdisease involves injections of

vWF or concentratesof factor VIII to which

vWF is attached. Another therapeutic ap-

proach is to administer a drug that in-

creasesvWF levels in the blood.

Hemophilia

Hemophilia(he¯-mo¯-ﬁl⬘e¯-a˘) isa genetic disor-

der in which clotting isabnormal or absent.

It’smost often found in people from northern

Europe and their descendants. Because he-

mophilia isan X-linked trait(see chapter 29),

itoccurs almost exclusively in males. Hemo-

philia A (classichemophilia) results from a

deﬁciencyof plasma coagulation factor VIII,

andhemophilia B is caused by a deﬁciency

in plasma factor IX. Hemophilia A occursin

approximately1 in 10,000 male births, and

hemophilia B occurs in approximately1 in

100,000 male births. Treatment of hemo-

philia involvesinjection of the missing clot-

ting factor taken from donated blood.

Thrombocytopenia

Thrombocytopenia (throm⬘bo¯-sı¯-to¯-pe¯⬘ne¯-a˘)

is a condition in which the number of

platelets is greatly reduced, resulting in

chronicbleeding through small vessels and

capillaries. Thrombocytopenia has several

causes, including increased plateletdestruc-

tion, caused by autoimmune disease (see

chapter 22) or infections, and decreased

platelet production, resulting from heredi-

tarydisorders, pernicious anemia, drug ther-

apy, radiation therapy, or leukemias.

Leukemia

The leukemiasare cancers of the red bone

marrow in which abnormal production of

one or more ofthe white blood cell typesoc-

cur. Because these cellsare usually imma-

ture or abnormal and lack their normal

immunologic functions, patients are very

susceptible to infections. The excesspro-

duction ofwhite blood cells in the red mar-

row can also interfere with red blood cell

and plateletformation and thus lead to ane-

mia and bleeding.

InfectiousDiseases of the Blood

Microorganisms don’t normallysur vive in

the blood. Blood can transportmicroorgan-

isms, however, and theycan multiply in the

blood. Microorganismscan enter the body

and be transported bythe blood to the tis-

sues they infect. For example, the po-

liomyelitis virus enters through the gas-

trointestinaltract and is carried to nervous

tissue. After microorganisms are estab-

lished ata site of infection, some can enter

the blood. Theycan then be transported to

other locationsin the body, multiply within

the blood, or be eliminated by the body’s

immune system.

Septicemia (sep-ti-se¯⬘me¯-a˘), or blood

poisoning, isthe spread of microorganisms

and their toxins bythe blood. Often sep-

ticemia resultsfrom the introduction of mi-

croorganismsby a medical procedure, such

asthe insertion of an intravenous tube into

a blood vessel. The release oftoxins by mi-

croorganisms can cause septic shock,

which isa decrease in blood pressure that

can resultin death.

In a few diseases, microorganismsac-

tually multiply within blood cells. Malaria

(ma˘-la¯r⬘e¯-a˘) is caused by a protozoan (Plas-

modium) that is introduced into the blood

bythe bite of the Anopheles mosquito. Part

ofthe development of the protozoan occurs

inside red blood cells. The symptoms of

chillsand fever in malaria are produced by

toxinsreleased when the protozoan causes

the red blood cells to rupture. Infec-

tiousmononucleosis (mon⬘o¯ -noo-kle¯-o¯⬘sis)

iscaused by a virus (Epstein-Barr virus) that

infects lymphocytes (B cells). The lympho-

cytes are altered by the virus, and the im-

mune system attacks and destroys the

lymphocytes. The immune system response

is believed to produce the symptoms of

fever, sore throat, and swollen lymph

nodes. Acquired immunodeﬁciency syn-

drome (AIDS) iscaused by the human im-

munodeﬁciency virus (HIV), which infects

lymphocytes and suppresses the immune

system (see chapter 22).

The presence ofmicroorganisms in the

blood isa concern with blood transfusions,

because it’spossible to infect the blood re-

cipient. Blood isroutinely tested, especially

for AIDSand hepatitis, in an effort to elimi-

nate this risk. Hepatitis (hep-a˘-tı¯⬘tis) is an

infection ofthe liver caused by several kinds

ofviruses. After recovering, hepatitisvictims

can become carriers. Although theyshow no

signsof the disease, they release the virus

into their blood or bile. To preventinfection

ofothers, anyone who has had hepatitis is

asked notto donate blood products.

SEM 2000x

Figure A

Sickle-CellDisease

Red blood cellsin a person with sickle-cell

disease appear normalin oxygenated blood. In

deoxygenated blood, hemoglobin changes

shape and causesthe cells to become sickle-

shaped and rigid.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Prothrombin Time Measurement

Prothrombin time measurement is a measure of how long it

takes for the blood to start clotting, which normally is 9–12 sec-

onds.Prothrombin time is determined by adding thromboplastin

to whole plasma.Thromboplastin is a chemical released from in-

jured tissues that starts the process of clotting (see ﬁgure 19.11).

Prothrombin time is ofﬁcially reported as the International Nor-

malized Ratio (INR), which standardizes the time it takes to clot

based on the slightly different thromboplastins used by different

labs.Because many clotting factors must be activated to form pro-

thrombin,a deﬁciency of any one of them can cause an abnormal

prothrombin time.Vitamin K deﬁciency,certain liver diseases, and

drug therapy can cause an increased prothrombin time.

Blood Chemistry

The composition of materials dissolved or suspended in the

plasma can be used to assess the functioning ofmany of the body’s

systems (Appendix E).For example, high blood glucose levels can

indicate that the pancreas is not producing enough insulin; high

blood urea nitrogen (BUN) can be a sign ofreduced kidney func-

tion;increased bilirubin can indicate liver dysfunction or hemoly-

Part4 Regulationsand Maintenance662

sis;and high cholesterol levels can indicate an increased risk of de-

veloping cardiovascular disease.A number of blood chemistry tests

are routinely done when a blood sample is taken,and additional

tests are available.

36. For each of the following tests, deﬁne the test and give an

example of a disorderthat would cause an abnormal test

result:

a. red blood count

b. hemoglobin measurement

c. hematocrit measurement

d. white blood count

e. differential white blood count

f. plateletcount

g. prothrombin time measurement

h. blood chemistry tests

PREDICT

When a patientcomplains of acute pain in the abdomen, the physician

suspectsappendicitis, which is often caused by a bacterialinfection

ofthe appendix. What blood test should be done to support the

diagnosis?

Functionsof Blood

(p. 640)

1. Blood transports gases,nutrients, waste products,and hor mones.

2. Blood is involved in the regulation ofhomeostasis and the

maintenance ofpH, body temperature, ﬂuid balance, and electrolyte

levels.

3. Blood protects against disease and blood loss.

Plasma

(p. 641)

1. Plasma is mostly water (91%) and contains proteins,such as

albumin (maintains osmotic pressure),globulins (function in

transport and immunity),ﬁbrinogen (involved in clot formation),

and hormones and enzymes (involved in regulation).

2. Plasma also contains ions,nutrients,waste products, and gases.

Formed Elements

(p. 642)

The formed elements include red blood cells (erythrocytes),white blood

cells (leukocytes),and platelets (cell fragments).

Production ofFormed Elements

1. In the embryo and fetus,the formed elements are produced in a

number oflocations.

2. After birth,red bone marrow becomes the source ofthe for med

elements.

3. All formed elements are derived from stem cells.

Red Blood Cells

1. Red blood cells are biconcave disks containing hemoglobin and

carbonic anhydrase.

• A hemoglobin molecule consists of four heme and four globin

molecules.The heme molecules transport oxygen, and the globin

molecules transport carbon dioxide and nitric oxide.Iron is

required for oxygen transport.

• Carbonic anhydrase is involved with the transport of carbon

dioxide.

2. Erythropoiesis is the production ofred blood cells.

• Stem cells in red bone marrow eventually give rise to late

erythroblasts,which lose their nuclei and are released into the

blood as reticulocytes.Loss of the endoplasmic reticulum by a

reticulocyte produces a red blood cell.

• In response to low blood oxygen,the kidneys produce

erythropoietin,which stimulates erythropoiesis.

3. Hemoglobin from ruptured red blood cells is phagocytized by

macrophages.The hemoglobin is broken down, and heme becomes

bilirubin,which is secreted in bile.

White Blood Cells

1. White blood cells protect the body against microorganisms and

remove dead cells and debris.

2. Five types ofwhite blood cells exist.

• Neutrophils are small phagocytic cells.

• Eosinophils function to reduce inﬂammation.

• Basophils release histamine and are involved with increasing the

inﬂammatory response.

• Lymphocytes are important in immunity,including the

production ofantibodies.

• Monocytes leave the blood,enter tissues, and become large

phagocytic cells called macrophages.

Platelets

Platelets,or thrombocytes, are cell fragments pinched off from megakary-

ocytes in the red bone marrow.

Hemostasis

(p. 650)

Hemostasis is very important to the maintenance ofhomeostasis.

Vascular Spasm

Vasoconstriction ofdamaged blood vessels reduces blood loss.

SUMMARY

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Chapter 19 Cardiovascular System: Blood 663

PlateletPlug Formation

1. Platelets repair minor damage to blood vessels by forming platelet

plugs.

• In platelet adhesion, platelets bind to collagen in damaged tissues.

• In the platelet release reaction,platelets release chemicals that

activate additional platelets.

• In platelet aggregation, platelets bind to one another to form a

platelet plug.

2. Platelets also release chemicals involved with coagulation.

Coagulation

1. Coagulation is the formation ofa blood clot.

2. Coagulation consists ofthree stages.

• Activation of prothrombinase.

• Conversion of prothrombin to thrombin by prothrombinase.

• Conversion of ﬁbrinogen to ﬁbrin by thrombin. The insoluble

ﬁbrin forms the clot.

3. The ﬁrst stage ofcoagulation occurs through the extrinsic or

intrinsic clotting pathway.Both pathways end with the production

ofprothrombinase.

• The extrinsic clotting pathway begins with the release of

thromboplastin from damaged tissues.

• The intrinsic clotting pathway begins with the activation of factor

XII.

Controlof Clot Formation

1. Heparin and antithrombin inhibit thrombin activity.Fibrinogen is,

therefore,not converted to ﬁbrin, and clot formation is inhibited.

2. Prostacyclin counteracts the effects ofthrombin.

ClotRetraction and Dissolution

1. Clot retraction results from the contraction ofplatelets, which pull

the edges ofdamaged tissue closer together.

2. Serum,which is plasma minus ﬁbrinogen and some clotting factors,

is squeezed out ofthe clot.

3. Factor XII,thrombin,tissue plasminogen activator, and urokinase

activate plasmin,which dissolves ﬁbrin (the clot).

Blood Grouping

(p. 655)

1. Blood groups are determined by antigens on the surface ofred

blood cells.

2. Antibodies can bind to red blood cell antigens,resulting in

agglutination or hemolysis ofred blood cells.

ABO Blood Group

1. Type A blood has A antigens,type B blood has B antigens,type AB

blood has A and B antigens,and type O blood has neither A nor B

antigens.

2. Type A blood has anti-B antibodies,type B blood has anti-A

antibodies,type AB blood has neither anti-A nor anti-B antibodies,

and type O blood has both anti-A and anti-B antibodies.

3. Mismatching the ABO blood group results in transfusion reactions.

Rh Blood Group

1. Rh-positive blood has certain Rh antigens (the D antigens),whereas

Rh-negative blood does not.

2. Antibodies against the Rh antigen are produced by an Rh-negative

person when the person is exposed to Rh-positive blood.

3. The Rh blood group is responsible for hemolytic disease ofthe

newborn.

DiagnosticBlood Tests

(p. 658)

Type and Crossmatch

Blood typing determines the ABO and Rh blood groups ofa blood sample.

A crossmatch tests for agglutination reactions between donor and recipi-

ent blood.

Complete Blood Count

The complete blood count consists ofthe following: red blood count, he-

moglobin measurement (grams of hemoglobin per 100 mL of blood),

hematocrit measurement (percent volume ofred blood cells), and white

blood count.

DifferentialWhite Blood Count

The differential white blood count determines the percentage ofeach type

ofwhite blood cell.

Clotting

Platelet count and prothrombin time measure the ability ofthe blood to

clot.

Blood Chemistry

The composition ofmaterials dissolved or suspended in plasma (e.g., glu-

cose,urea nitrogen, bilirubin, and cholesterol) can be used to assess the

functioning and status ofthe body’s systems.

1. Which ofthese is a function of blood?

a. clot formation

b. protection against foreign substances

c. maintenance ofbody temperature

d. regulation of pH and osmosis

e. all ofthe above

2. Which ofthese is not a component of plasma?

a. nitrogen

b. sodium ions

c. platelets

d. water

e. urea

3. Which ofthese plasma proteins plays an important role in

maintaining the osmotic concentration ofthe blood?

a. albumin

b. ﬁbrinogen

c. platelets

d. hemoglobin

e. globulins

4. The cells that give rise to the red blood cells are

a. lymphoblasts.

b. megakaryoblasts.

c. monoblasts.

d. myeloblasts.

e. proerythroblasts.

REVIEW AND COMPREHENSION

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

5. Red blood cells

a. are the least numerous formed element in the blood.

b. are phagocytic cells.

c. are produced in the yellow marrow.

d. do not have a nucleus.

e. all ofthe above.

6. Given these ways oftransporting carbon dioxide in the blood:

1. bicar bonate ions

2. combined with blood proteins

3. dissolved in plasma

Choose the arrangement that lists them in the correct order from

largest to smallest percentage ofcarbon dioxide transported.

a. 1,2, 3

b. 1, 3, 2

c. 2,3, 1

d. 2, 1, 3

e. 3,1, 2

7. Which ofthese components of a red blood cell is correctly matched

with its function?

a. heme group ofhemoglobin—oxygen transport

b. globin portion of hemoglobin—carbon dioxide transport

c. carbonic anhydrase—carbon dioxide transport

d. cysteine on ␤-globin—nitric oxide transport

e. all ofthe above

8. Each hemoglobin molecule can become associated with

oxygen molecules.

a. one

b. two

c. three

d. four

e. unlimited

9. Which ofthese substances is not required for normal red blood cell

production?

a. folate

b. vitamin K

c. iron

d. vitamin B

10. Erythropoietin

a. is produced mainly by the heart.

b. inhibits the production of red blood cells.

c. production increases when blood oxygen decreases.

d. production is inhibited by testosterone.

e. all ofthe above.

11. Which ofthese changes occurs in the blood in response to the

initiation ofa vigorous exercise program?

a. increased erythropoietin production

b. increased concentration of reticulocytes

c. decreased bilirubin formation

d. both a and b

e. all ofthe above

12. Which ofthe components of hemoglobin is correctly matched with

its fate following the destruction ofa red blood cell?

a. heme:reused to form a new hemoglobin molecule

b. globin: broken down into amino acids

c. iron:mostly secreted in bile

d. all of the above

13. Ifyou live near sea level and are training for a track meet in Denver

(5280 ft elevation),you would want to spend a few weeks before the

meet training at

a. sea level.

b. an altitude similar to Denver’s.

c. a facility with a hyperbaric chamber.

d. any location—it doesn’t matter.

Part4 Regulationsand Maintenance664

14. The blood cells that function to inhibit inﬂammation are

a. eosinophils.

b. basophils.

c. neutrophils.

d. monocytes.

e. lymphocytes.

15. The most numerous type ofwhite blood cell, whose primary

function is phagocytosis,is

a. eosinophils.

b. basophils.

c. neutrophils.

d. monocytes.

e. lymphocytes.

16. Monocytes

a. are the smallest white blood cells.

b. increase in number during chronic infections.

c. give rise to neutrophils.

d. produce antibodies.

17. The white blood cells that release large amounts ofhistamine and

heparin are

a. eosinophils.

b. basophils.

c. neutrophils.

d. monocytes.

e. lymphocytes.

18. The smallest white blood cells,which include B cells and T cells,are

a. eosinophils.

b. basophils.

c. neutrophils.

d. monocytes.

e. lymphocytes.

19. Platelets

a. are derived from megakaryocytes.

b. are cell fragments.

c. have surface molecules that attach to collagen.

d. play an important role in clot formation.

e. all ofthe above.

20. Given these processes in platelet plug formation:

1. platelet adhesion

2. platelet aggregation

3. platelet release reaction

Choose the arrangement that lists the processes in the correct order

after a blood vessel is damaged.

a. 1,2, 3

b. 1, 3, 2

c. 3,1, 2

d. 3, 2, 1

e. 2,3, 1

21. A constituent ofblood plasma that forms the network of ﬁbers in a

clot is

a. ﬁbrinogen.

b. tissue factor.

c. platelets.

d. thrombin.

e. prothrombinase.

22. Given these chemicals:

1. activated factor XII

2. ﬁbr inogen

3. prothrombinase

4. thrombin

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Chapter 19 Cardiovascular System: Blood 665

Choose the arrangement that lists the chemicals in the order they

are used during clot formation.

a. 1,3, 4,2

b. 2, 3, 4, 1

c. 3,2, 1,4

d. 3, 1, 2, 4

e. 3,4, 2,1

23. The extrinsic clotting pathway

a. begins with the release ofthromboplastin (tissue factor).

b. leads to the production of prothrombinase.

c. requires Ca

2⫹

d. all of the above.

24. Which ofthese is not an anticoagulant found in the blood?

a. ethylenediamenetetraacetic acid (EDTA)

b. antithrombin

c. heparin

d. prostacyclin

25. The chemical that is involved in the breakdown ofa clot

(ﬁbrinolysis) is

a. antithrombin.

b. ﬁbrinogen.

c. heparin.

d. plasmin.

e. sodium citrate.

26. A person with type A blood

a. has anti-A antibodies.

b. has type B antigens.

c. will have a transfusion reaction ifgiven type B blood.

d. all of the above.

27. In the United States,the most common blood type is

a. A positive.

b. B positive.

c. O positive.

d. O negative.

e. AB negative.

28. Rh-negative mothers who receive a RhoGAM injection are given

that injection to

a. initiate the synthesis ofanti-Rh antibodies in the mother.

b. initiate anti-Rh antibody production in the baby.

c. prevent the mother from producing anti-Rh antibodies.

d. prevent the baby from producing anti-Rh antibodies.

29. The blood test that distinguishes between leukocytosis and

leukopenia is

a. type and crossmatch.

b. hematocrit.

c. platelet count.

d. complete blood count.

e. prothrombin time measurement.

30. An elevated neutrophil count is usually indicative of

a. an allergic reaction.

b. a bacterial infection.

c. a viral infection.

d. a parasitic infection.

e. increased antibody production.

Answers in Appendix F

1. In hereditary hemolytic anemia,massive destruction of red blood

cells occurs.Would you expect the reticulocyte count to be above or

below normal? Explain why one ofthe symptoms of the disease is

jaundice.In 1910, it was discovered that hereditary hemolytic

anemia could be successfully treated by removing the spleen.

Explain why this treatment is effective.

2. Red Packer,a physical education major,wanted to improve his

performance in an upcoming marathon race.About 6 weeks before

the race,500 mL of blood was removed from his body,and the

formed elements were separated from the plasma.The formed

elements were frozen,and the plasma was reinfused into his body.

Just before the competition,the formed elements were thawed and

injected into his body.Explain why this procedure,called blood

doping or blood boosting,would help Red’s performance. Can you

suggest any possible bad effects?

3. Chemicals like benzene and chloramphenicol can destroy red bone

marrow and cause aplastic anemia.What symptoms develop as a

result ofthe lack of (a) red blood cells, (b) platelets, and (c) white

blood cells?

4. Some people habitually use barbiturates to depress feelings of

anxiety.Barbiturates cause hypoventilation, which is a slower-than-

normal rate ofbreathing, because they suppress the respiratory

centers in the brain.What happens to the red blood count of a

habitual user ofbarbiturates? Explain.

5. What blood problems would you expect to observe in a patient after

total gastrectomy (removal ofthe stomach)? Explain.

6. According to the old saying,“Good food makes good blood.”Name

three substances in the diet that are essential for “good blood.”What

blood disorders develop ifthese substances are absent from the diet?

Answers in Appendix G

CRITICAL THINKING

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

IV. Regulations and

Maintenance

19. Cardiovascular System:

Blood

Companies, 2004

Part4 Regulationsand Maintenance666

1. The reason fetal hemoglobin must be more effective at binding

oxygen than adult hemoglobin is so that the fetal circulation can

draw the needed oxygen away from the maternal circulation.If

maternal blood had an equal or greater oxygen afﬁnity,the fetal

blood would not be able to draw away the required oxygen,and the

fetus would die.

2. An elevated reticulocyte count indicates that erythropoiesis and the

demand for red blood cells are increased and that immature red

blood cells (reticulocytes) are entering the circulation in large

numbers.An elevated reticulocyte count can occur for a number of

reasons,including loss of blood; therefore, after a person donates a

unit ofblood, the reticulocyte count increases.

3. Carbon monoxide binds to the iron ofhemoglobin and prevents the

transport ofoxygen. The decreased oxygen stimulates the release of

erythropoietin,which increases red blood cell production in red

bone marrow,thereby causing the number of red blood cells in the

blood to increase.

4. The white blood cells shown in ﬁgure 19.8 are (a) lymphocyte,

(b)basophil, (c) monocyte, (d) neutrophil, and (e) eosinophil.

5. Platelets become activated at sites oftissue damage, which is the

location where it’s advantageous to form a clot to stop bleeding.

6. People with type AB blood were called universal recipients because

they could receive type A,B, AB,or O blood with little likelihood of

a transfusion reaction.Type AB blood does not have antibodies

against type A or B antigens;therefore, transfusion of these antigens

in type A,B, or AB blood does not cause a transfusion reaction in a

person with type AB blood.The term is misleading, however, for

two reasons.First, other blood groups can cause a transfusion

reaction.Second, antibodies in the donor’s blood can cause a

transfusion reaction.For example, type O blood contains anti-A and

anti-B antibodies that can react against the A and B antigens in type

AB blood.

7. A white blood count (WBC) should be done.An elevated WBC,

leukocytosis,can be an indication of bacterial infections. A

differential WBC should also be done.An increase in the number of

neutrophils supports the diagnosis ofa bacterial infection. Coupled

with other symptoms,this could mean appendicitis. If these tests are

normal,appendicitis is still a possibility and the physician must rely

on other clinical signs.Diagnostic accuracy for appendicitis is

approximately 75%–85% for experienced physicians.

ANSWERS TO PREDICT QUESTIONS

Visitthe Online Learning Center at www.mhhe.com/seeley6 for

chapter quizzes, interactive learning exercises, and other studytools.