endocrine and more

Question Figure 9–A
CHAPTER 10
The Endocrine System
221
222
CHAPTER 10
Chapter Outline
Chemistry of Hormones
Regulation of Hormone Secretion
The Pituitary Gland
Posterior Pituitary Gland
Antidiuretic hormone
Oxytocin
Anterior Pituitary Gland
Growth hormone
Thyroid-stimulating hormone
Adrenocorticotropic hormone
Prolactin
Follicle-stimulating hormone
Luteinizing hormone
Thyroid Gland
Thyroxine and T3
Calcitonin
Parathyroid Glands
Parathyroid Hormone
Pancreas
Glucagon
Insulin
Adrenal Glands
Adrenal Medulla
Epinephrine and norepinephrine
Adrenal Cortex
Aldosterone
Cortisol
Ovaries
Estrogen
Progesterone
Inhibin
Testes
Testosterone
Inhibin
Other Hormones
Prostaglandins
Mechanisms of Hormone Action
The Two-Messenger Mechanism—Protein
Hormones
Action of Steroid Hormones
Aging and the Endocrine System
BOX 10–1 DISORDERS OF GROWTH HORMONE
BOX 10–2 DISORDERS OF THYROXINE
BOX 10–3 DIABETES MELLITUS
BOX 10–4 DISORDERS OF THE ADRENAL CORTEX
Student Objectives
• Name the endocrine glands and the hormones
secreted by each.
• Explain how a negative feedback mechanism
works.
• Explain how the hypothalamus is involved
in the secretion of hormones from the posterior
pituitary gland and anterior pituitary
gland.
• State the functions of oxytocin and antidiuretic
hormone, and explain the stimulus for secretion
of each.
• State the functions of the hormones of the anterior
pituitary gland, and state the stimulus for
secretion of each.
The Endocrine System
223
Student Objectives (Continued)
• State the functions of thyroxine and T3, and
describe the stimulus for their secretion.
• Explain how parathyroid hormone and calcitonin
work as antagonists.
• Explain how insulin and glucagon work as antagonists.
• State the functions of epinephrine and norepinephrine,
and explain their relationship to the sympathetic
division of the autonomic nervous system.
• State the functions of aldosterone and cortisol, and
describe the stimulus for secretion of each.
• State the functions of estrogen, progesterone,
testosterone, and inhibin and state the stimulus for
secretion of each.
• Explain what prostaglandins are made of, and state
some of their functions.
• Explain how the protein hormones are believed to
exert their effects.
• Explain how the steroid hormones are believed to
exert their effects.
New Terminology
Alpha cells (AL-fah SELLS)
Beta cells (BAY-tah SELLS)
Catecholamines (KAT-e-kohl-ah-MEENZ)
Corpus luteum (KOR-pus LOO-tee-um)
Gluconeogenesis (GLOO-koh-nee-oh-JEN-i-sis)
Glycogenesis (GLIGH-koh-JEN-i-sis)
Glycogenolysis (GLIGH-ko-jen-OL-i-sis)
Hypercalcemia (HIGH-per-kal-SEE-mee-ah)
Hyperglycemia (HIGH-per-gligh-SEE-mee-ah)
Hypocalcemia (HIGH-poh-kal-SEE-mee-ah)
Hypoglycemia (HIGH-poh-gligh-SEE-mee-ah)
Hypophysis (high-POFF-e-sis)
Islets of Langerhans (EYE-lets of LAHNG-er-hanz)
Prostaglandins (PRAHS-tah-GLAND-ins)
Renin-angiotensin mechanism (REE-nin AN-jeeoh-
TEN-sin)
Sympathomimetic (SIM-pah-tho-mi-MET-ik)
Target organ (TAR-get OR-gan)
Related Clinical Terminology
Acromegaly (AK-roh-MEG-ah-lee)
Addison’s disease (ADD-i-sonz)
Cretinism (KREE-tin-izm)
Cushing’s syndrome (KOOSH-ingz SIN-drohm)
Diabetes mellitus (DYE-ah-BEE-tis mel-LYE-tus)
Giantism (JIGH-an-tizm)
Goiter (GOY-ter)
Graves’ disease (GRAYVES)
Ketoacidosis (KEY-toh-ass-i-DOH-sis)
Myxedema (MIK-suh-DEE-mah)
Pituitary dwarfism (pi-TOO-i-TER-ee DWORFizm)
Terms that appear in bold type in the chapter text are defined in the glossary, which begins on page 547.
We have already seen how the nervous system
regulates body functions by means of nerve impulses
and integration of information by the spinal cord and
brain. The other regulating system of the body is
the endocrine system, which consists of endocrine
glands that secrete chemicals called hormones. These
glands, and the names of the hormones they secrete,
are shown in Fig. 10–1.
Endocrine glands are ductless; that is, they do not
have ducts to take their secretions to specific sites.
224 The Endocrine System
Anterior: GH, TSH, ACTH
FSH, LH, Prolactin
Posterior: ADH, Oxytocin
Melatonin
PTH
Releasing hormones
for anterior pituitary
Thyroxine and T3
Calcitonin
THYMUS GLAND
Immune hormones
Insulin
Glucagon
Cortex: Aldosterone
Cortisol
Sex hormones
Medulla: Epinephrine
Norepinephrine
Testosterone
Inhibin
THYROID GLAND
HYPOTHALAMUS
PITUITARY (HYPOPHYSIS) GLAND
PINEAL GLAND
PARATHYROID GLANDS
ADRENAL (SUPRARENAL) GLANDS
PANCREAS
OVARIES
Estrogen
Progesterone
Inhibin
TESTES
Figure 10–1. The endocrine system. Locations of many endocrine glands. Both male
and female gonads (testes and ovaries) are shown.
QUESTION: Why is the location of the thyroid gland not really important for its function?
Instead, hormones are secreted directly into capillaries
and circulate in the blood throughout the body. Each
hormone then exerts very specific effects on certain
organs, called target organs or target tissues. Some
hormones, such as insulin and thyroxine, have many
target organs. Other hormones, such as calcitonin and
some pituitary gland hormones, have only one or a
few target organs.
In general, the endocrine system and its hormones
help regulate growth, the use of foods to produce
energy, resistance to stress, the pH of body fluids and
fluid balance, and reproduction. In this chapter we will
discuss the specific functions of the hormones and
how each contributes to homeostasis.
CHEMISTRY OF HORMONES
With respect to their chemical structure, hormones
may be classified into three groups: amines, proteins,
and steroids.
1. Amines—these simple hormones are structural
variations of the amino acid tyrosine. This group
includes thyroxine from the thyroid gland and epinephrine
and norepinephrine from the adrenal
medulla.
2. Proteins—these hormones are chains of amino
acids. Insulin from the pancreas, growth hormone
from the anterior pituitary gland, and calcitonin
from the thyroid gland are all proteins. Short
chains of amino acids may be called peptides.
Antidiuretic hormone and oxytocin, synthesized by
the hypothalamus, are peptide hormones.
3. Steroids—cholesterol is the precursor for the
steroid hormones, which include cortisol and aldosterone
from the adrenal cortex, estrogen and progesterone
from the ovaries, and testosterone from
the testes.
REGULATION OF
HORMONE SECRETION
Hormones are secreted by endocrine glands when
there is a need for them, that is, for their effects on
their target organs. The cells of endocrine glands
respond to changes in the blood or perhaps to other
hormones in the blood. These stimuli are the information
they use to increase or decrease secretion of
their own hormones. When a hormone brings about
its effects, the stimulus is reversed, and secretion of
the hormone decreases until the stimulus reoccurs.
You may recall from Chapter 1 that this is a negative
feedback mechanism, and the mechanism for thyroxine
was depicted in Fig. 1–3. Let us use insulin as a different
example here.
Insulin is secreted by the pancreas when the blood
glucose level is high; that is, hyperglycemia is the
stimulus for secretion of insulin. Once circulating
in the blood, insulin enables cells to remove glucose
from the blood so that it can be used for energy
production and enables the liver to store glucose
as glycogen. As a result of these actions of insulin,
the blood glucose level decreases, reversing the stimulus
for secretion of insulin. Insulin secretion then
decreases until the blood glucose level increases
again.
In any hormonal negative feedback mechanism,
information about the effects of the hormone is “fed
back” to the gland, which then decreases its secretion
of the hormone. This is why the mechanism is called
“negative”: The effects of the hormone reverse the
stimulus and decrease the secretion of the hormone.
The secretion of many other hormones is regulated in
a similar way.
The hormones of the anterior pituitary gland are
secreted in response to releasing hormones (also
called releasing factors) secreted by the hypothalamus.
You may recall this from Chapter 8. Growth hormone,
for example, is secreted in response to growth hormone–
releasing hormone (GHRH) from the hypothalamus.
As growth hormone exerts its effects, the
secretion of GHRH decreases, which in turn decreases
the secretion of growth hormone. This is another type
of negative feedback mechanism.
For each of the hormones to be discussed in this
chapter, the stimulus for its secretion will also be mentioned.
Some hormones function as an antagonistic
pair to regulate a particular aspect of blood chemistry;
these mechanisms will also be covered.
THE PITUITARY GLAND
The pituitary gland (or hypophysis) hangs by a short
stalk (infundibulum) from the hypothalamus and is
enclosed by the sella turcica of the sphenoid bone.
The Endocrine System 225
226 The Endocrine System
Figure 10–2. Hormones of the pituitary gland and their target organs.
QUESTION: Which pituitary hormones have other endocrine glands as their target organs?
Despite its small size, the pituitary gland regulates
many body functions. Its two major portions are the
posterior pituitary gland (neurohypophysis), which is
an extension of the nerve tissue of the hypothalamus,
and the anterior pituitary gland (adenohypophysis),
which is separate glandular tissue. All of the hormones
of the pituitary gland and their target organs are
shown in Fig. 10–2. It may be helpful for you to look
at this summary picture before you begin reading the
following sections.
POSTERIOR PITUITARY GLAND
The two hormones of the posterior pituitary gland
are actually produced by the hypothalamus and simply
stored in the posterior pituitary until needed. Their
release is stimulated by nerve impulses from the hypothalamus
(Fig. 10–3).
Antidiuretic Hormone
Antidiuretic hormone (ADH, also called vasopressin)
increases the reabsorption of water by kidney
tubules, which decreases the amount of urine formed.
The water is reabsorbed into the blood, so as urinary
output is decreased, blood volume is increased, which
helps maintain normal blood pressure. ADH also
decreases sweating, but the amount of water conserved
is much less than that conserved by the kidneys.
The stimulus for secretion of ADH is decreased
water content of the body. If too much water is lost
through sweating or diarrhea, for example, osmoreceptors
in the hypothalamus detect the increased
“saltiness” of body fluids. The hypothalamus then
transmits impulses to the posterior pituitary to
increase the secretion of ADH and decrease the loss of
more water in urine.
Any type of dehydration stimulates the secretion of
ADH to conserve body water. In the case of severe
hemorrhage, ADH is released in large amounts and
will also cause vasoconstriction, especially in arterioles,
which will help to raise or at least maintain blood
pressure. This function gives ADH its other name,
vasopressin.
Ingestion of alcohol inhibits the secretion of ADH
and increases urinary output. If alcohol intake is excessive
and fluid is not replaced, a person will feel thirsty
and dizzy the next morning. The thirst is due to the
loss of body water, and the dizziness is the result of
low blood pressure.
The Endocrine System 227
Hypothalamus
Releasing hormones
Capillaries in hypothalamus
Hypophyseal portal veins
Capillaries in
anterior pituitary
Hormones of
anterior pituitary
Lateral hypophyseal vein
Superior hypophyseal
arteries
Optic chiasma
B
Hypothalamus
Hypothalamic-hypophyseal tract
Posterior pituitary
Inferior hypophyseal
artery
Hormones of
posterior
pituitary
Posterior lobe vein
Optic chiasma
A
Figure 10–3. Structural relationships of hypothalamus and pituitary gland. (A) Posterior
pituitary stores hormones produced in the hypothalamus. (B) Releasing hormones of the
hypothalamus circulate directly to the anterior pituitary and influence its secretions. Notice
the two networks of capillaries.
QUESTION: In part A, name the hormones of the posterior pituitary. In part B, what stimulates
secretion of anterior pituitary hormones?
Oxytocin
Oxytocin stimulates contraction of the uterus at the
end of pregnancy and stimulates release of milk from
the mammary glands.
As labor begins, the cervix of the uterus is
stretched, which generates sensory impulses to the
hypothalamus, which in turn stimulates the posterior
pituitary to release oxytocin. Oxytocin then causes
strong contractions of the smooth muscle (myometrium)
of the uterus to bring about delivery of the
baby and the placenta. The secretion of oxytocin is
one of the few positive feedback mechanisms within
the body, and the external brake or shutoff of the
feedback cycle is delivery of the baby and the placenta.
It has been discovered that the placenta itself
secretes oxytocin at the end of gestation and in an
amount far higher than that from the posterior pituitary
gland. Research is continuing to determine the
exact mechanism and precise role of the placenta in
labor.
When a baby is breast-fed, the sucking of the baby
stimulates sensory impulses from the mother’s nipple
to the hypothalamus. Nerve impulses from the hypothalamus
to the posterior pituitary cause the release of
oxytocin, which stimulates contraction of the smooth
muscle cells around the mammary ducts. This release
of milk is sometimes called the “milk let-down” reflex.
The hormones of the posterior pituitary are summarized
in Table 10–1.
Both ADH and oxytocin are peptide hormones
with similar structure, having nine amino acids each.
And both have been found to influence aspects of
behavior such as nurturing and trustfulness. Certain
brain cells have receptors for vasopressin, and they
seem to be involved in creating the bonds that sustain
family life. Trust is part of many social encounters
such as friendship, school, sports and games, and buying
and selling, as well as family life. These two small
hormones seem to have some influence on us mentally
as well as physically.
ANTERIOR PITUITARY GLAND
The hormones of the anterior pituitary gland regulate
many body functions. They are in turn regulated
by releasing hormones from the hypothalamus.
These releasing hormones are secreted into capillaries
in the hypothalamus and pass through the hypophyseal
portal veins to another capillary network in the
anterior pituitary gland. Here, the releasing hormones
are absorbed and stimulate secretion of the anterior
pituitary hormones. This small but specialized pathway
of circulation is shown in Fig. 10–3. This pathway
permits the releasing hormones to rapidly stimulate
the anterior pituitary, without having to pass through
general circulation.
Growth Hormone
Growth hormone (GH) is also called somatotropin,
and it does indeed promote growth (see Fig. 10–4).
GH stimulates cells to produce insulin-like growth factors
(IGFs), intermediary molecules that bring about
the functions of GH. Growth hormone increases the
transport of amino acids into cells, and increases the
rate of protein synthesis. Amino acids cannot be stored
in the body, so when they are available, they must be
228 The Endocrine System
Table 10–1 HORMONES OF THE POSTERIOR PITUITARY GLAND
Hormone Function(s) Regulation of Secretion
Antidiuretic hormone
(ADH or vasopressin)
Oxytocin
• Increases water reabsorption
by the kidney tubules (water
returns to the blood)
• Decreases sweating
• Causes vasoconstriction
(in large amounts)
• Promotes contraction of
myometrium of uterus (labor)
• Promotes release of milk from
mammary glands
Decreased water content in the body (alcohol
inhibits secretion)
Nerve impulses from hypothalamus, the result of
stretching of cervix or stimulation of nipple
Secretion from placenta at end of gestation—
stimulus unknown
used in protein synthesis. Excess amino acids are
changed to carbohydrates or fat, for energy storage.
Growth hormone ensures that amino acids will be used
for whatever protein synthesis is necessary, before the
amino acids can be changed to carbohydrates. Growth
hormone also stimulates cell division in those tissues
capable of mitosis. These functions contribute to the
growth of the body during childhood, especially
growth of bones and muscles.
You may now be wondering if GH is secreted in
adults, and the answer is yes. The use of amino acids
for the synthesis of proteins is still necessary. Even if
the body is not growing in height, some tissues will
require new proteins for repair or replacement. GH
also stimulates the release of fat from adipose tissue
and the use of fats for energy production. This is
important any time we go for extended periods without
eating, no matter what our ages.
The secretion of GH is regulated by two releasing
hormones from the hypothalamus. Growth hormone–
releasing hormone (GHRH), which increases the
secretion of GH, is produced during hypoglycemia
and during exercise. Another stimulus for GHRH is a
high blood level of amino acids; the GH then secreted
will ensure the conversion of these amino acids into
protein. Somatostatin may also be called growth hormone
inhibiting hormone (GHIH), and, as its name
tells us, it decreases the secretion of GH. Somatostatin
is produced during hyperglycemia. Disorders of GH
secretion are discussed in Box 10–1.
The Endocrine System 229
Increases use of
fats for energy
Increases protein
synthesis
Increases
mitosis
Bone and
muscle
Liver and
other viscera
ATP
GH
Anterior
pituitary
Figure 10–4. Functions of growth hormone.
QUESTION: Which functions of growth hormone directly help bones and muscles to
grow?
Thyroid-Stimulating Hormone
Thyroid-stimulating hormone (TSH) is also called
thyrotropin, and its target organ is the thyroid gland.
TSH stimulates the normal growth of the thyroid and
the secretion of thyroxine (T4) and triiodothyronine
(T3). The functions of these thyroid hormones will be
covered later in this chapter.
The secretion of TSH is stimulated by thyrotropinreleasing
hormone (TRH) from the hypothalamus.
When metabolic rate (energy production) decreases,
TRH is produced.
Adrenocorticotropic Hormone
Adrenocorticotropic hormone (ACTH) stimulates
the secretion of cortisol and other hormones by the
adrenal cortex. Secretion of ACTH is increased by
corticotropin-releasing hormone (CRH) from the
hypothalamus. CRH is produced in any type of physiological
stress situation such as injury, disease, exercise,
or hypoglycemia (being hungry is stressful).
Prolactin
Prolactin, as its name suggests, is responsible for lactation.
More precisely, prolactin initiates and maintains
milk production by the mammary glands. The
regulation of secretion of prolactin is complex, involving
both prolactin-releasing hormone (PRH) and
prolactin-inhibiting hormone (PIH) from the hypothalamus.
The mammary glands must first be acted
upon by other hormones such as estrogen and progesterone,
which are secreted in large amounts by the
placenta during pregnancy. Then, after delivery of the
baby, prolactin secretion increases and milk is produced.
If the mother continues to breast-feed, prolactin
levels remain high.
Follicle-Stimulating Hormone
Follicle-stimulating hormone (FSH) is one of the
gonadotropic hormones; that is, it has its effects on
the gonads: the ovaries or testes. FSH is named for
one of its functions in women. Within the ovaries are
ovarian follicles that contain potential ova (egg cells).
FSH stimulates the growth of ovarian follicles; that is,
it initiates egg development in cycles of approximately
28 days. FSH also stimulates secretion of estrogen by
the follicle cells. In men, FSH initiates sperm production
within the testes.
The secretion of FSH is stimulated by the hypothalamus,
which produces gonadotropin-releasing
hormone (GnRH). FSH secretion is decreased by
inhibin, a hormone produced by the ovaries or testes.
Luteinizing Hormone
Luteinizing hormone (LH) is another gonadotropic
hormone. In women, LH is responsible for ovulation,
the release of a mature ovum from an ovarian follicle.
LH then stimulates that follicle to develop into the
corpus luteum, which secretes progesterone, also
under the influence of LH. In men, LH stimulates the
interstitial cells of the testes to secrete testosterone.
230 The Endocrine System
BOX 10–1 DISORDERS OF GROWTH HORMONE
not have this condition; they are tall as a result of
their genetic makeup and good nutrition.
In an adult, hypersecretion of GH is caused by a
pituitary tumor, and results in acromegaly. The
long bones cannot grow because the epiphyseal
discs are closed, but the growth of other bones is
stimulated. The jaw and other facial bones become
disproportionately large, as do the bones of the
hands and feet. The skin becomes thicker, and the
tongue also grows and may protrude. Other consequences
include compression of nerves by abnormally
growing bones and growth of the articular
cartilages, which then erode and bring on arthritis.
Treatment of acromegaly requires surgical removal
of the tumor or its destruction by radiation.
A deficiency or excess of growth hormone (GH)
during childhood will have marked effects on the
growth of a child. Hyposecretion of GH results in
pituitary dwarfism, in which the person may
attain a final height of only 3 to 4 feet but will have
normal body proportions. GH can now be produced
using genetic engineering and may be used
to stimulate growth in children with this disorder.
GH will not increase growth of children with the
genetic potential for short stature. Reports that GH
will reverse the effects of aging are simply not true.
Hypersecretion of GH results in giantism (or
gigantism), in which the long bones grow excessively
and the person may attain a height of 8 feet.
Most very tall people, such as basketball players, do
(LH is also called ICSH, interstitial cell stimulating
hormone.)
Secretion of LH is also regulated by GnRH from
the hypothalamus. We will return to FSH and LH, as
well as a discussion of the sex hormones, in Chapter
20.
The hormones of the anterior pituitary are summarized
in Table 10–2.
THYROID GLAND
The thyroid gland is located on the front and sides of
the trachea just below the larynx. Its two lobes are
connected by a middle piece called the isthmus. The
structural units of the thyroid gland are thyroid follicles,
which produce thyroxine (T4) and triiodothyronine
(T3). Iodine is necessary for the synthesis of
these hormones; thyroxine contains four atoms of
iodine, and T3 contains three atoms of iodine.
The third hormone produced by the thyroid
gland is calcitonin, which is secreted by parafollicular
cells. Its function is very different from those
of thyroxine and T3, which you may recall from
Chapter 6.
THYROXINE AND T3
Thyroxine (T4) and T3 have the same functions: regulation
of energy production and protein synthesis,
which contribute to growth of the body and to normal
body functioning throughout life (Fig. 10–5). Thyroxine
and T3 increase cell respiration of all food types
(carbohydrates, fats, and excess amino acids) and
thereby increase energy and heat production. They
also increase the rate of protein synthesis within cells.
Normal production of thyroxine and T3 is essential for
physical growth, normal mental development, and
maturation of the reproductive system. These hormones
are the most important day-to-day regulators
of metabolic rate; their activity is reflected in the func-
The Endocrine System 231
Table 10–2 HORMONES OF THE ANTERIOR PITUITARY GLAND
Hormone Function(s) Regulation of Secretion
Growth hormone (GH)
Thyroid-stimulating
hormone (TSH)
Adrenocorticotropic
hormone (ACTH)
Prolactin
Follicle-stimulating
hormone (FSH)
Luteinizing hormone
(LH) (ICSH)
• Increases rate of mitosis
• Increases amino acid transport into cells
• Increases rate of protein synthesis
• Increases use of fats for energy
• Increases secretion of thyroxine and T3
by thyroid gland
• Increases secretion of cortisol by the
adrenal cortex
• Stimulates milk production by the mammary
glands
In women:
• Initiates growth of ova in ovarian follicles
• Increases secretion of estrogen by follicle
cells
In men:
• Initiates sperm production in the testes
In women:
• Causes ovulation
• Causes the ruptured ovarian follicle to
become the corpus luteum
• Increases secretion of progesterone by
the corpus luteum
In men:
• Increases secretion of testosterone by
the interstitial cells of the testes
GHRH (hypothalamus) stimulates secretion
GHIH—somatostatin (hypothalamus)
inhibits secretion
TRH (hypothalamus)
CRH (hypothalamus)
PRH (hypothalamus) stimulates secretion
PIH (hypothalamus) inhibits secretion
GnRH (hypothalamus) stimulates secretion
Inhibin (ovaries or testes) inhibits secretion
GnRH (hypothalamus)
tioning of the brain, muscles, heart, and virtually all
other organs. Although thyroxine and T3 are not vital
hormones, in that they are not crucial to survival, their
absence greatly diminishes physical and mental
growth and abilities (see Box 10–2: Disorders of
Thyroxine).
Secretion of thyroxine and T3 is stimulated by
thyroid-stimulating hormone (TSH) from the anterior
pituitary gland (see also Fig. 1–3). When the
metabolic rate (energy production) decreases, this
change is detected by the hypothalamus, which
secretes thyrotropin releasing hormone (TRH). TRH
stimulates the anterior pituitary to secrete TSH,
which stimulates the thyroid to release thyroxine and
T3, which raise the metabolic rate by increasing
energy production. This negative feedback mechanism
then shuts off TRH from the hypothalamus until
the metabolic rate decreases again.
232 The Endocrine System
Thyroid gland
T4 and T3
Increase
cell respiration of
all foods
Increase
protein synthesis
Glucose
Fats
Excess
amino acids
ATP
Bone and muscle
Liver and viscera
Brain
Reproductive
organs
Figure 10–5. Functions of thyroxine and T3.
QUESTION: Which functions of thyroxine help bones and muscles to grow and maintain
their own functions?
CALCITONIN
Calcitonin decreases the reabsorption of calcium
and phosphate from the bones to the blood, thereby
lowering blood levels of these minerals. This function
of calcitonin helps maintain normal blood levels
of calcium and phosphate and also helps maintain
a stable, strong bone matrix. It is believed that
calcitonin exerts its most important effects during
childhood, when bones are growing. A form of calcitonin
obtained from salmon is used to help treat
osteoporosis.
The stimulus for secretion of calcitonin is hypercalcemia,
that is, a high blood calcium level. When
blood calcium is high, calcitonin ensures that no more
calcium will be removed from bones until there is a
real need for more calcium in the blood (Fig. 10–6).
The hormones of the thyroid gland are summarized in
Table 10–3.
PARATHYROID GLANDS
There are four parathyroid glands: two on the back
of each lobe of the thyroid gland (Fig. 10–7). The hormone
they produce is called parathyroid hormone.
PARATHYROID HORMONE
Parathyroid hormone (PTH) is an antagonist to calcitonin
and is important for the maintenance of normal
blood levels of calcium and phosphate. The target
organs of PTH are the bones, small intestine, and kidneys.
PTH increases the reabsorption of calcium and
phosphate from bones to the blood, thereby raising
their blood levels. Absorption of calcium and phosphate
from food in the small intestine, which also
requires vitamin D, is increased by PTH. This too
raises the blood levels of these minerals. In the kidneys,
PTH stimulates the activation of vitamin D and
increases the reabsorption of calcium and the excretion
of phosphate (more than is obtained from bones).
Therefore, the overall effect of PTH is to raise the
blood calcium level and lower the blood phosphate
level. The functions of PTH are summarized in Table
10–4.
Secretion of PTH is stimulated by hypocalcemia,
a low blood calcium level, and inhibited by hypercalcemia.
The antagonistic effects of PTH and calcitonin
are shown in Fig. 10–6. Together, these hormones
maintain blood calcium within a normal range.
Calcium in the blood is essential for the process of
blood clotting and for normal activity of neurons and
muscle cells.
As you might expect, a sustained hypersecretion of
PTH, such as is caused by a parathyroid tumor, would
remove calcium from bones and weaken them. It has
been found, however, that an intermittent, brief excess
of PTH, such as can occur by injection, will stimulate
the formation of more bone matrix, rather than matrix
reabsorption. This may seem very strange—the opposite
of what we would expect—but it shows how much
we have yet to learn about the body. PTH is being
investigated as a possible way to help prevent osteoporosis.
PANCREAS
The pancreas is located in the upper left quadrant of
the abdominal cavity, extending from the curve of the
duodenum to the spleen. Although the pancreas is
both an exocrine (digestive) gland as well as an
endocrine gland, only its endocrine function will
be discussed here. The hormone-producing cells of
the pancreas are called islets of Langerhans (pancre-
The Endocrine System 233
Table 10–3 HORMONES OF THE THYROID GLAND
Regulation
Hormone Function(s) of Secretion
Thyroxine (T4) and
triiodothyronine (T3)
Calcitonin
• Increase energy production from all food types
• Increase rate of protein synthesis
• Decreases the reabsorption of calcium and phosphate
from bones to blood
TSH (anterior pituitary)
Hypercalcemia
234 The Endocrine System
Bones
Ca+2 is retained in bone matrix
Accelerates calcium
absorption by bones
Hypercalcemia (high blood calcium)
Thyroid
Calcitonin Inhibits
Bones
Small intestine
Reabsorb Ca+2 to the blood
Hypocalcemia (low blood calcium)
Parathyroids
PTH
Kidneys
(vitamin D activated)
Figure 10–6. Calcitonin and parathyroid hormone (PTH) and their functions related to
the maintenance of the blood calcium level.
QUESTION: Which hormone helps keep calcium in bones? What vitamin does PTH help
activate, and where?
Table 10–4 HORMONE OF THE PARATHYROID GLANDS
Regulation
Hormone Functions of Secretion
Parathyroid hormone
(PTH)
• Increases the reabsorption of calcium and phosphate
from bone to blood
• Increases absorption of calcium and phosphate by
the small intestine
• Increases the reabsorption of calcium and the excretion
of phosphate by the kidneys; activates vitamin D
Hypocalcemia stimulates secretion.
Hypercalcemia inhibits
secretion.
atic islets; see Fig. 16–7); they contain alpha cells
that produce glucagon and beta cells that produce
insulin.
GLUCAGON
Glucagon stimulates the liver to change glycogen to
glucose (this process is called glycogenolysis, which
literally means “glycogen breakdown”) and to increase
the use of fats and excess amino acids for energy production.
The process of gluconeogenesis (literally,
“making new glucose”) is the conversion of excess
amino acids into simple carbohydrates that may enter
the reactions of cell respiration. The overall effect of
glucagon, therefore, is to raise the blood glucose level
and to make all types of food available for energy
production.
The secretion of glucagon is stimulated by hypoglycemia,
a low blood glucose level. Such a state may
occur between meals or during physiological stress situations
such as exercise (Fig. 10–8).
INSULIN
Insulin increases the transport of glucose from the
blood into cells by increasing the permeability of
cell membranes to glucose. (Brain, liver, and kidney
cells, however, are not dependent on insulin for
glucose intake.) Once inside cells, glucose is used in
The Endocrine System 235
Larynx
Thyroid
Parathyroid
glands
Trachea
Figure 10–7. Parathyroid glands in posterior view, on
lobes of the thyroid gland.
QUESTION: Which of the target organs of PTH may be
called a reservoir, and what do they store?
BOX 10–2 DISORDERS OF THYROXINE
(energy production) decreases, resulting in lethargy,
muscular weakness, slow heart rate, a feeling of
cold, weight gain, and a characteristic puffiness of
the face. The administration of thyroid hormones
will return the metabolic rate to normal.
Graves’ disease is an autoimmune disorder
that causes hypersecretion of thyroxine. The
autoantibodies seem to bind to TSH receptors on
the thyroid cells and stimulate secretion of excess
thyroxine. The symptoms are those that would be
expected when the metabolic rate is abnormally
elevated: weight loss accompanied by increased
appetite, increased sweating, fast heart rate, feeling
of warmth, and fatigue. Also present may be goiter
and exophthalmos, which is protrusion of the eyes.
Treatment is aimed at decreasing the secretion of
thyroxine by the thyroid, and medications or
radioactive iodine may be used to accomplish this.
Iodine is an essential component of thyroxine (and
T3), and a dietary deficiency of iodine causes goiter.
In an attempt to produce more thyroxine, the
thyroid cells become enlarged, and hence the thyroid
gland enlarges and becomes visible on the
front of the neck. The use of iodized salt has made
goiter a rare condition in many parts of the world.
Hyposecretion of thyroxine in a newborn has
devastating effects on the growth of the child.
Without thyroxine, physical growth is diminished,
as is mental development. This condition is called
cretinism, characterized by severe physical and
mental retardation. If the thyroxine deficiency is
detected shortly after birth, the child may be
treated with thyroid hormones to promote normal
development.
Hyposecretion of thyroxine in an adult is called
myxedema. Without thyroxine, the metabolic rate
cell respiration to produce energy. The liver and skeletal
muscles also change glucose to glycogen (glycogenesis,
which means “glycogen production”) to be
stored for later use. Insulin is also important in the
metabolism of other food types; it enables cells to take
in fatty acids and amino acids to use in the synthesis of
lipids and proteins (not energy production). Without
insulin, blood levels of lipids tend to rise and cells accumulate
excess fatty acids. With respect to blood glucose,
insulin decreases its level by promoting the use of
glucose for energy production. The antagonistic functions
of insulin and glucagon are shown in Fig. 10–8.
Insulin is a vital hormone; we cannot survive for
very long without it. A deficiency of insulin or in its
functioning is called diabetes mellitus, which is discussed
in Box 10–3: Diabetes Mellitus.
Secretion of insulin is stimulated by hyperglycemia,
a high blood glucose level. This state
occurs after eating, especially of meals high in carbohydrates.
As glucose is absorbed from the small intestine
into the blood, insulin is secreted to enable cells
to use the glucose for immediate energy. At the same
time, any excess glucose will be stored in the liver and
muscles as glycogen.
You will also notice in Fig. 16–7 the cells called
delta cells. These produce the hormone somatostatin,
which is identical to growth hormone–inhibiting hormone
from the hypothalamus. Pancreatic somatostatin
acts locally to inhibit the secretion of insulin and
glucagon, and it seems to slow the absorption of the
end products of digestion in the small intestine. The
hormones of the pancreas are summarized in Table
10–5.
ADRENAL GLANDS
The two adrenal glands are located one on top of
each kidney, which gives them their other name of
suprarenal glands. Each adrenal gland consists of two
parts: an inner adrenal medulla and an outer adrenal
cortex. The hormones produced by each part have
very different functions.
ADRENAL MEDULLA
The cells of the adrenal medulla secrete epinephrine
and norepinephrine, which collectively are called catecholamines
and are sympathomimetic. The secre-
236 The Endocrine System
Hyperglycemia
(High blood glucose)
Glucagon Liver
Liver changes
glycogen to
glucose and
converts amino
acids to
carbohydrates
Pancreas
Hypoglycemia
(Low blood glucose)
Cells use glucose
for energy production
Insulin
Cells
Liver
Skeletal
muscles
Liver and skeletal
muscles change
glucose to glycogen
Figure 10–8. Insulin and
glucagon and their functions
related to the maintenance of
the blood glucose level.
QUESTION: Which hormone
enables cells to use glucose
for energy production? What
is the stimulus for secretion of
this hormone?
The Endocrine System 237
tion of both hormones is stimulated by sympathetic
impulses from the hypothalamus, and their functions
duplicate and prolong those of the sympathetic division
of the autonomic nervous system (mimetic means
“to mimic”).
Epinephrine and Norepinephrine
Epinephrine (Adrenalin) and norepinephrine (noradrenalin)
are both secreted in stress situations and
help prepare the body for “fight or flight.” Norepinephrine
is secreted in small amounts, and its most
significant function is to cause vasoconstriction in the
skin, viscera, and skeletal muscles (that is, throughout
the body), which raises blood pressure.
Epinephrine, secreted in larger amounts, increases
the heart rate and force of contraction and stimulates
vasoconstriction in skin and viscera and vasodilation in
skeletal muscles. It also dilates the bronchioles,
decreases peristalsis, stimulates the liver to change
glycogen to glucose, increases the use of fats for
energy, and increases the rate of cell respiration. Many
of these effects do indeed seem to be an echo of sympathetic
responses, don’t they? Responding to stress is
so important that the body acts redundantly (that is,
exceeds what is necessary, or repeats itself) and has
both a nervous mechanism and a hormonal mechanism.
Epinephrine is actually more effective than sympathetic
stimulation, however, because the hormone
increases energy production and cardiac output to a
greater extent. The hormones of the adrenal medulla
are summarized in Table 10–6, and their functions are
shown in Fig. 10–9.
ADRENAL CORTEX
The adrenal cortex secretes three types of steroid
hormones: mineralocorticoids, glucocorticoids, and
Table 10–5 HORMONES OF THE PANCREAS
Regulation
Hormone Functions of Secretion
Glucagon
(alpha cells)
Insulin (beta cells)
Somatostatin
(delta cells)
• Increases conversion of glycogen to glucose in the liver
• Increases the use of excess amino acids and of fats for energy
• Increases glucose transport into cells and the use of glucose for
energy production
• Increases the conversion of excess glucose to glycogen in the liver
and muscles
• Increases amino acid and fatty acid transport into cells, and their
use in synthesis reactions
• Decreases secretion of insulin and glucagon
• Slows absorption of nutrients
Hypoglycemia
Hyperglycemia
Rising levels of insulin
and glucagon
Table 10–6 HORMONES OF THE ADRENAL MEDULLA
Regulation
Hormone Function(s) of Secretion
Norepinephrine
Epinephrine
• Causes vasoconstriction in skin, viscera, and skeletal muscles
• Increases heart rate and force of contraction
• Dilates bronchioles
• Decreases peristalsis
• Increases conversion of glycogen to glucose in the liver
• Causes vasodilation in skeletal muscles
• Causes vasoconstriction in skin and viscera
• Increases use of fats for energy
• Increases the rate of cell respiration
Sympathetic impulses
from the hypothalamus
in stress
situations
238 The Endocrine System
BOX 10–3 DIABETES MELLITUS
more water is lost as well, symptoms include
greater urinary output (polyuria) and thirst (polydipsia).
The long-term effects of hyperglycemia produce
distinctive vascular changes. The capillary walls
thicken, and exchange of gases and nutrients
diminishes. The most damaging effects are seen in
the skin (especially of the feet), the retina (diabetic
retinopathy), and the kidneys. Poorly controlled
diabetes may lead to dry gangrene, blindness, and
severe kidney damage. Atherosclerosis is common,
because faulty triglyceride metabolism is linked to
faulty glucose metabolism. Neuropathy (damage to
nerves) leads to impaired cutaneous sensation and
difficulty with fine movements, such as buttoning a
shirt. It is now possible for diabetics to prevent
much of this tissue damage by precise monitoring
of the blood glucose level and more frequent
administration of insulin. Insulin pumps are able to
more closely mimic the natural secretion of insulin.
A very serious potential problem for the type 1
diabetic is ketoacidosis. When glucose cannot be
used for energy, the body turns to fats and proteins,
which are converted by the liver to ketones.
Ketones are organic acids (acetone, acetoacetic
acid) that can be used in cell respiration, but cells
are not able to utilize them rapidly so ketones
accumulate in the blood. Ketones are acids, and
lower the pH of the blood as they accumulate. The
kidneys excrete excess ketones, but in doing so
excrete more water as well, which leads to dehydration
and worsens the acidosis. Without administration
of insulin to permit the use of glucose, and
IV fluids to restore blood volume to normal, ketoacidosis
will progress to coma and death.
There are two types of diabetes mellitus: Type 1
is called insulin-dependent diabetes and its onset is
usually in childhood (juvenile onset). Type 2
is called non–insulin-dependent diabetes, and its
onset is usually later in life (maturity onset).
Type 1 diabetes is characterized by destruction
of the beta cells of the islets of Langerhans and a
complete lack of insulin (see Box Figure 10–A);
onset is usually abrupt. Destruction of the beta cells
is an autoimmune response, perhaps triggered by a
virus. There may be a genetic predisposition,
because certain HLA types are found more frequently
in type 1 diabetics than in other children
(see Box 11–5: HLA). Insulin by injection (inhaled
insulin is undergoing clinical trials) is essential to
control type 1 diabetes. Research is continuing on
the use of immunosuppressant medications to try
to preserve some beta cells (if diagnosis is early),
and also on the transplantation of stem cells to
replace lost beta cells.
In type 2 diabetes, insulin is produced but cannot
exert its effects on cells because of a loss of
insulin receptors on cell membranes (see Box Figure
10–A). Onset of type 2 diabetes is usually gradual,
and risk factors include a family history of diabetes
and being overweight. Control may not require
insulin, but rather medications that enable insulin
to react with the remaining membrane receptors.
For those with a family history of diabetes, a low-fat
diet and regular exercise reduce the risk of developing
the disease. The commitment to exercise
must be lifelong but is well worth the effort,
because diabetes is very destructive.
Without insulin (or its effects) blood glucose level
remains high, and glucose is lost in urine. Since
A Normal B Type 1 C Type 2
Glucose
Insulin
Insulin Receptor
Box Figure 10–A (A) Cell membrane in normal state, with insulin receptors and
insulin to regulate glucose intake. (B) Cell membrane in type 1 diabetes: insulin not
present, glucose remains outside cell. (C) Cell membrane in type 2 diabetes: without
insulin receptors, glucose remains outside cell.
The Endocrine System 239
Norepinephrine Epinephrine
Dilates bronchioles
Increases conversion
of
glycogen to glucose
Increases use of
fats for energy
Increases cell
respiration
Increases rate and
force of contraction
Vasoconstriction
in skin
Vasoconstriction
in viscera
Decreases
peristalsis
Vasodilation
in
skeletal muscle
Vasoconstriction in
skeletal muscle
Adrenal medulla
Figure 10–9. Functions of epinephrine and norepinephrine.
QUESTION: Do epinephrine and norepinephrine have the same effect on skeletal muscle?
Explain your answer.
sex hormones. The sex hormones, “female” estrogens
and “male” androgens (similar to testosterone), are
produced in very small amounts, and their importance
is not known with certainty. They may contribute to
rapid body growth during early puberty. They may
also be important in supplying estrogen to women
after menopause and to men throughout life (see the
“Estrogen” section later in this chapter).
The functions of the other adrenal cortical hormones
are well known, however, and these are considered
vital hormones.
Aldosterone
Aldosterone is the most abundant of the mineralocorticoids,
and we will use it as a representative of this
group of hormones. The target organs of aldosterone
are the kidneys, but there are important secondary
effects as well. Aldosterone increases the reabsorption
of sodium and the excretion of potassium by the kidney
tubules. Sodium ions (Na ) are returned to the
blood, and potassium ions (K ) are excreted in urine.
Look at Fig. 10–10 as you read the following.
As Na ions are reabsorbed, hydrogen ions (H )
may be excreted in exchange. This is one mechanism
to prevent the accumulation of excess H ions, which
would cause acidosis of body fluids. Also, as Na ions
are reabsorbed, negative ions such as chloride (Cl )
and bicarbonate (HCO3
–) follow the Na ions back to
the blood, and water follows by osmosis. This indirect
effect of aldosterone, the reabsorption of water by the
kidneys, is very important to maintain normal blood
volume and blood pressure. In summary, then, aldosterone
maintains normal blood levels of sodium and
potassium, and contributes to the maintenance of normal
blood pH, blood volume, and blood pressure.
A number of factors stimulate the secretion of
aldosterone. These are a deficiency of sodium, loss of
blood or dehydration that lowers blood pressure, or an
elevated blood level of potassium. Low blood pressure
or blood volume activates the renin-angiotensin
mechanism of the kidneys. This mechanism is discussed
in Chapters 13 and 18, so we will say for now
that the process culminates in the formation of a
chemical called angiotensin II. Angiotensin II causes
vasoconstriction and stimulates the secretion of aldosterone
by the adrenal cortex. Aldosterone then
increases sodium and water retention by the kidneys
to help restore blood volume and blood pressure to
normal.
Cortisol
We will use cortisol as a representative of the group
of hormones called glucocorticoids, because it is
responsible for most of the actions of this group
(Fig. 10–11). Cortisol increases the use of fats and
excess amino acids (gluconeogenesis) for energy and
decreases the use of glucose. This is called the glucosesparing
effect, and it is important because it conserves
240 The Endocrine System
Adrenal cortex
Aldosterone
K+ ions
excreted
Na+ ions
reabsorbed
HCO3
– ions reabsorbed
H2O reabsorbed
H+ ions excreted
Blood volume,
blood pressure,
and pH are
maintained
Figure 10–10. Functions of aldosterone. Direct and indirect functions are shown.
QUESTION: What ions does aldosterone have a direct effect on, and what is the effect?
glucose for use by the brain. Cortisol is secreted in any
type of physiological stress situation: disease, physical
injury, hemorrhage, fear or anger, exercise, and
hunger. Although most body cells easily use fatty acids
and excess amino acids in cell respiration, brain cells
do not, so they must have glucose. By enabling other
cells to use the alternative energy sources, cortisol
ensures that whatever glucose is present will be available
to the brain.
Cortisol also has an anti-inflammatory effect.
During inflammation, histamine from damaged tissues
makes capillaries more permeable, and the lysosomes
of damaged cells release their enzymes, which
help break down damaged tissue but may also cause
destruction of nearby healthy tissue. Cortisol blocks
the effects of histamine and stabilizes lysosomal membranes,
preventing excessive tissue destruction.
Inflammation is a beneficial process up to a point, and
is an essential first step if tissue repair is to take place.
It may, however, become a vicious cycle of damage,
inflammation, more damage, more inflammation,
and so on—a positive feedback mechanism. Normal
cortisol secretion seems to be the brake, to limit
the inflammation process to what is useful for tissue
repair, and to prevent excessive tissue destruction.
Too much cortisol, however, decreases the immune
response, leaving the body susceptible to infection
and significantly slowing the healing of damaged
tissue (see Box 10–4: Disorders of the Adrenal
Cortex).
The Endocrine System 241
Adrenal cortex
Cortisol
Conserves
glucose
Limits
inflammation
Increases use of
excess
amino acids
Increases use
of fats
ATP
ATP
Adipose tissue
Amino acids
Glucose
Brain
Glycogen
Liver
Most tissues
Figure 10–11. Functions of cortisol.
QUESTION: Which food types will be used for energy by most tissues? Which food type
may be stored?
The direct stimulus for cortisol secretion is ACTH
from the anterior pituitary gland, which in turn is
stimulated by corticotropin releasing hormone (CRH)
from the hypothalamus. CRH is produced in the
physiological stress situations mentioned earlier.
Although we often think of epinephrine as a hormone
important in stress, cortisol is also important. The
hormones of the adrenal cortex are summarized in
Table 10–7.
OVARIES
The ovaries are located in the pelvic cavity, one on
each side of the uterus. The hormones produced by
the ovaries are the steroids estrogen and progesterone,
and the protein inhibin. Although their functions are
an integral part of Chapters 20 and 21, we will briefly
discuss some of them here.
242 The Endocrine System
Table 10–7 HORMONES OF THE ADRENAL CORTEX
Hormone Functions Regulation of Secretion
Aldosterone
Cortisol
• Increases reabsorption of Na ions by
the kidneys to the blood
• Increases excretion of K ions by the
kidneys in urine
• Increases use of fats and excess amino
acids for energy
• Decreases use of glucose for energy
(except for the brain)
• Increases conversion of glucose to
glycogen in the liver
• Anti-inflammatory effect: stabilizes lysosomes
and blocks the effects of histamine
Low blood Na level
Low blood volume or blood pressure
High blood K level
ACTH (anterior pituitary) during
physiological stress
BOX 10–4 DISORDERS OF THE ADRENAL CORTEX
The cause may be a pituitary tumor that increases
ACTH secretion or a tumor of the adrenal cortex
itself.
Excessive cortisol promotes fat deposition in the
trunk of the body, while the extremities remain
thin. The skin becomes thin and fragile, and healing
after injury is slow. The bones also become fragile
because osteoporosis is accelerated. Also characteristic
of this syndrome is the rounded appearance of
the face. Treatment is aimed at removal of the cause
of the hypersecretion, whether it be a pituitary or
adrenal tumor.
Cushing’s syndrome may also be seen in people
who receive corticosteroids for medical reasons.
Transplant recipients or people with rheumatoid
arthritis or severe asthma who must take corticosteroids
may exhibit any of the above symptoms. In
such cases, the disadvantages of this medication
must be weighed against the benefits provided.
Addison’s disease is the result of hyposecretion of
the adrenol cortical hormones. Most cases are idiopathic,
that is, of unknown cause; atrophy of the
adrenal cortex decreases both cortisol and aldosterone
secretion.
Deficiency of cortisol is characterized by hypoglycemia,
decreased gluconeogenesis, and depletion
of glycogen in the liver. Consequences are
muscle weakness and the inability to resist physiological
stress. Aldosterone deficiency leads to retention
of potassium and excretion of sodium and
water in urine. The result is severe dehydration, low
blood volume, and low blood pressure. Without
treatment, circulatory shock and death will follow.
Treatment involves administration of hydrocortisone;
in high doses this will also compensate for the
aldosterone deficiency.
Cushing’s syndrome is the result of hypersecretion
of the adrenal cortex, primarily cortisol.
The Endocrine System 243
ESTROGEN
Estrogen is secreted by the follicle cells of the ovary;
secretion is stimulated by FSH from the anterior pituitary
gland. Estrogen promotes the maturation of the
ovum in the ovarian follicle and stimulates the growth
of blood vessels in the endometrium (lining) of the
uterus in preparation for a possible fertilized egg.
The secondary sex characteristics in women also
develop in response to estrogen. These include
growth of the duct system of the mammary glands,
growth of the uterus, and the deposition of fat subcutaneously
in the hips and thighs. The closure of the
epiphyseal discs in long bones is brought about by
estrogen, and growth in height stops. Estrogen is also
believed to lower blood levels of cholesterol and triglycerides.
For women before the age of menopause
this is beneficial in that it decreases the risk of atherosclerosis
and coronary artery disease.
Research suggests that estrogen no longer be considered
only a “female” hormone. Estrogen seems to
have effects on many organs, including the brain, the
heart, and blood vessels. In the brain, testosterone
from the testes or the adrenal cortex can be converted
to estrogen, which may be important for memory,
especially for older people. Estrogen seems to have
non-reproductive functions in both men and women,
although we cannot yet be as specific as we can be
with the reproductive functions in women, mentioned
previously.
PROGESTERONE
When a mature ovarian follicle releases an ovum, the
follicle becomes the corpus luteum and begins to
secrete progesterone in addition to estrogen. This is
stimulated by LH from the anterior pituitary gland.
Progesterone promotes the storage of glycogen
and the further growth of blood vessels in the endometrium,
which thus becomes a potential placenta.
The secretory cells of the mammary glands also
develop under the influence of progesterone.
Both progesterone and estrogen are secreted by the
placenta during pregnancy; these functions are covered
in Chapter 21.
INHIBIN
The corpus luteum secretes another hormone, called
inhibin. Inhibin helps decrease the secretion of FSH
by the anterior pituitary gland, and GnRH by the
hypothalamus.
TESTES
The testes are located in the scrotum, a sac of skin
between the upper thighs. Two hormones, testosterone
and inhibin, are secreted by the testes.
TESTOSTERONE
Testosterone is a steroid hormone secreted by the
interstitial cells of the testes; the stimulus for secretion
is LH from the anterior pituitary gland.
Testosterone promotes maturation of sperm in the
seminiferous tubules of the testes; this process begins
at puberty and continues throughout life. At puberty,
testosterone stimulates development of the male secondary
sex characteristics. These include growth of
all the reproductive organs, growth of facial and body
hair, growth of the larynx and deepening of the voice,
and growth (protein synthesis) of the skeletal muscles.
Testosterone also brings about closure of the epiphyses
of the long bones.
INHIBIN
The hormone inhibin is secreted by the sustentacular
cells of the testes; the stimulus for secretion is
increased testosterone. The function of inhibin is to
decrease the secretion of FSH by the anterior pituitary
gland. The interaction of inhibin, testosterone, and
the anterior pituitary hormones maintains spermatogenesis
at a constant rate.
OTHER HORMONES
Melatonin is a hormone produced by the pineal
gland, which is located at the back of the third ventricle
of the brain. The secretion of melatonin is greatest
during darkness and decreases when light enters the
eye and the retina signals the hypothalamus. A recent
discovery is that the retina also produces melatonin,
which seems to indicate that the eyes and pineal gland
work with the biological clock of the hypothalamus. In
other mammals, melatonin helps regulate seasonal
reproductive cycles. For people, melatonin definitely
stimulates the onset of sleep and increases its duration.
244 The Endocrine System
Other claims, such as that melatonin strengthens the
immune system or prevents cellular damage and
aging, are without evidence as yet.
There are other organs that produce hormones that
have only one or a few target organs. For example, the
stomach and duodenum produce hormones that regulate
aspects of digestion and appetite. Adipose tissue
produces the appetite-suppressing hormone leptin.
The thymus gland produces hormones necessary for
the normal functioning of the immune system, and the
kidneys produce a hormone that stimulates red blood
cell production. All of these will be discussed in later
chapters.
PROSTAGLANDINS
Prostaglandins (PGs) are made by virtually all cells
from the phospholipids of their cell membranes. They
differ from other hormones in that they do not circulate
in the blood to target organs, but rather exert
their effects locally, where they are produced.
There are many types of prostaglandins, designated
by the letters A through I, as in PGA, PGB, and so on.
Prostaglandins have many functions, and we will list
only a few of them here. Prostaglandins are known to
be involved in inflammation, pain mechanisms, blood
clotting, vasoconstriction and vasodilation, contraction
of the uterus, reproduction, secretion of digestive
glands, and nutrient metabolism. Current research
is directed at determining the normal functioning of
prostaglandins in the hope that many of them may
eventually be used clinically.
One familiar example may illustrate the widespread
activity of prostaglandins. For minor pain such as a
headache, many people take aspirin. Aspirin inhibits
the synthesis of prostaglandins involved in pain mechanisms
and usually relieves the pain. Some people,
however, such as those with rheumatoid arthritis, may
take large amounts of aspirin to diminish pain and
inflammation. These people may bruise easily because
blood clotting has been impaired. This too is an effect
of aspirin, which blocks the synthesis of prostaglandins
necessary for blood clotting.
MECHANISMS OF
HORMONE ACTION
Exactly how hormones exert their effects on their target
organs involves a number of complex processes,
which will be presented simply here.
A hormone must first bond to a receptor for it on
or in the target cell. Cells respond to certain hormones
and not to others because of the presence of
specific receptors, which are proteins. These receptor
proteins may be part of the cell membrane or within
the cytoplasm or nucleus of the target cells. A hormone
will affect only those cells that have its specific
receptors. Liver cells, for example, have cell membrane
receptors for insulin, glucagon, growth hormone,
and epinephrine; bone cells have receptors for
growth hormone, PTH, and calcitonin. Cells of the
ovaries and testes do not have receptors for PTH and
calcitonin, but do have receptors for FSH and LH,
which bone cells and liver cells do not have. Once a
hormone has bonded to a receptor on or in its target
cell, other reactions will take place.
THE TWO-MESSENGER MECHANISM—
PROTEIN HORMONES
The two-messenger mechanism of hormone action
involves “messengers” that make something happen,
that is, stimulate specific reactions. Protein hormones
usually bond to receptors of the cell membrane,
and the hormone is called the first messenger.
The hormone–receptor bonding activates the enzyme
adenyl cyclase on the inner surface of the cell membrane.
Adenyl cyclase synthesizes a substance called
cyclic adenosine monophosphate (cyclic AMP or
cAMP) from ATP, and cyclic AMP is the second messenger.
Cyclic AMP activates specific enzymes within the
cell, which bring about the cell’s characteristic
response to the hormone. These responses include a
change in the permeability of the cell membrane to a
specific substance, an increase in protein synthesis,
activation of other enzymes, or the secretion of a cellular
product.
In summary, a cell’s response to a hormone is determined
by the enzymes within the cell, that is, the reactions
of which the cell is capable. These reactions are
brought about by the first messenger, the hormone,
which stimulates the formation of the second messenger,
cyclic AMP. Cyclic AMP then activates the cell’s
enzymes to elicit a response to the hormone (Fig.
10–12).
ACTION OF STEROID HORMONES
Steroid hormones are soluble in the lipids of the cell
membrane and diffuse easily into a target cell. Once
The Endocrine System 245
inside the cell, the steroid hormone combines with a
protein receptor in the cytoplasm, and this steroidprotein
complex enters the nucleus of the cell. Within
the nucleus, the steroid-protein complex activates specific
genes, which begin the process of protein synthesis.
The enzymes produced bring about the cell’s
characteristic response to the hormone (see Fig.
10–12).
AGING AND THE
ENDOCRINE SYSTEM
Most of the endocrine glands decrease their secretions
with age, but normal aging usually does not lead to
serious hormone deficiencies. There are decreases in
adrenol cortical hormones, for example, but the levels
are usually sufficient to maintain homeostasis of water,
electrolytes, and nutrients. The decreased secretion of
growth hormone leads to a decrease in muscle mass
and an increase in fat storage. A lower basal metabolic
rate is common in elderly people as the thyroid slows
its secretion of thyroxine. Unless specific pathologies
develop, however, the endocrine system usually continues
to function adequately in old age.
SUMMARY
The hormones of endocrine glands are involved in virtually
all aspects of normal body functioning. The
growth and repair of tissues, the utilization of food to
produce energy, responses to stress, the maintenance
of the proper levels and pH of body fluids, and the
continuance of the human species all depend on hormones.
Some of these topics will be discussed in later
chapters. As you might expect, you will be reading
about the functions of many of these hormones again
and reviewing their important contributions to the
maintenance of homeostasis.
A
B
Figure 10–12. Mechanisms
of hormone action. (A) Twomessenger
mechanism of the
action of protein hormones.
(B) Action of steroid hormones.
See text for description.
QUESTION: What must a cell
have in order to be a target cell
for a particular hormone?
246 The Endocrine System
Endocrine glands are ductless glands that
secrete hormones into the blood. Hormones
exert their effects on target organs or tissues.
Chemistry of Hormones
1. Amines—structural variations of the amino acid
tyrosine; thyroxine, epinephrine.
2. Proteins—chains of amino acids; peptides are short
chains. Insulin, GH, glucagon are proteins; ADH
and oxytocin are peptides.
3. Steroids—made from cholesterol; cortisol, aldosterone,
estrogen, testosterone.
Regulation of Hormone Secretion
1. Hormones are secreted when there is a need for
their effects. Each hormone has a specific stimulus
for secretion.
2. The secretion of most hormones is regulated by
negative feedback mechanisms: As the hormone
exerts its effects, the stimulus for secretion is
reversed, and secretion of the hormone decreases.
Pituitary Gland (Hypophysis)—hangs from
hypothalamus by the infundibulum; enclosed
by sella turcica of sphenoid bone (see Figs.
10–1 and 10–2)
1. Posterior Pituitary (Neurohypophysis)—stores
hormones produced by the hypothalamus (Figs.
10–2 and 10–3 and Table 10–1).
• ADH—increases water reabsorption by the kidneys,
decreases sweating, in large amounts causes
vasoconstriction. Result: decreases urinary output
and increases blood volume; increases BP.
Stimulus: nerve impulses from hypothalamus
when body water decreases.
• Oxytocin—stimulates contraction of myometrium
of uterus during labor and release of milk
from mammary glands. Stimulus: nerve impulses
from hypothalamus as cervix is stretched or as
infant sucks on nipple.
2. Anterior Pituitary (Adenohypophysis)—secretions
are regulated by releasing hormones from the
hypothalamus (Fig. 10–3 and Table 10–2).
• GH—through intermediary molecules, IGFs,
GH increases amino acid transport into cells
and increases protein synthesis; increases rate
of mitosis; increases use of fats for energy
(Fig. 10–4). Stimulus: GHRH from the hypothalamus.
• TSH—increases secretion of thyroxine and T3
by the thyroid. Stimulus: TRH from the hypothalamus.
• ACTH—increases secretion of cortisol by the
adrenal cortex. Stimulus: CRH from the hypothalamus.
• Prolactin—initiates and maintains milk production
by the mammary glands. Stimulus: PRH
from the hypothalamus.
• FSH—In women: initiates development of ova in
ovarian follicles and secretion of estrogen by follicle
cells.
In men: initiates sperm development in the testes.
Stimulus: GnRH from the hypothalamus.
• LH—In women: stimulates ovulation, transforms
mature follicle into corpus luteum and stimulates
secretion of progesterone.
In men: stimulates secretion of testosterone by
the testes. Stimulus: GnRH from the hypothalamus.
Thyroid Gland—on front and sides of trachea
below the larynx (see Fig. 10–1 and
Table 10–3)
• Thyroxine (T4) and T3—(Fig. 10–5) produced by
thyroid follicles. Increase use of all food types for
energy and increase protein synthesis. Necessary
for normal physical, mental, and sexual development.
Stimulus: TSH from the anterior pituitary.
• Calcitonin—produced by parafollicular cells.
Decreases reabsorption of calcium from bones
and lowers blood calcium level. Stimulus: hypercalcemia.
Parathyroid Glands—four; two on posterior
of each lobe of thyroid (see Figs. 10–6 and
10–7 and Table 10–4)
• PTH—increases reabsorption of calcium and
phosphate from bones to the blood; increases
absorption of calcium and phosphate by the
small intestine; increases reabsorption of calcium
and excretion of phosphate by the kidneys, and
activates vitamin D. Result: raises blood calcium
and lowers blood phosphate levels. Stimulus:
hypocalcemia. Inhibitor: hypercalcemia.
STUDY OUTLINE
Pancreas—extends from curve of duodenum
to the spleen. Islets of Langerhans contain
alpha cells and beta cells (see Figs. 10–1 and
10–8 and Table 10–5)
• Glucagon—secreted by alpha cells. Stimulates
liver to change glycogen to glucose; increases use
of fats and amino acids for energy. Result: raises
blood glucose level. Stimulus: hypoglycemia.
• Insulin—secreted by beta cells. Increases use of
glucose by cells to produce energy; stimulates
liver and muscles to change glucose to glycogen;
increases cellular intake of fatty acids and amino
acids to use for synthesis of lipids and proteins.
Result: lowers blood glucose level. Stimulus: hyperglycemia.
• Somatostatin—inhibits secretion of insulin and
glucagon.
Adrenal Glands—one on top of each kidney;
each has an inner adrenal medulla and an
outer adrenal cortex (see Fig. 10–1)
1. Adrenal Medulla—produces catecholamines in
stress situations (Table 10–6 and Fig. 10–9).
• Norepinephrine—stimulates vasoconstriction
and raises blood pressure.
• Epinephrine—increases heart rate and force,
causes vasoconstriction in skin and viscera and
vasodilation in skeletal muscles; dilates bronchioles;
slows peristalsis; causes liver to change
glycogen to glucose; increases use of fats for
energy; increases rate of cell respiration. Stimulus:
sympathetic impulses from the hypothalamus.
2. Adrenal Cortex—produces mineralocorticoids,
glucocorticoids, and very small amounts of sex hormones
(function not known with certainty) (Table
10–7).
• Aldosterone—(Fig. 10–10) increases reabsorption
of sodium and excretion of potassium by
the kidneys. Results: hydrogen ions are excreted
in exchange for sodium; chloride and bicarbonate
ions and water follow sodium back to the
blood; maintains normal blood pH, blood volume,
and blood pressure. Stimulus: decreased
blood sodium or elevated blood potassium;
decreased blood volume or blood pressure (activates
the renin-angiotensin mechanism of the
kidneys).
• Cortisol—(Fig. 10–11) increases use of fats and
amino acids for energy; decreases use of glucose
to conserve glucose for the brain; anti-inflammatory
effect: blocks effects of histamine and stabilizes
lysosomes to prevent excessive tissue
damage. Stimulus: ACTH from hypothalamus
during physiological stress.
Ovaries—in pelvic cavity on either side of
uterus (see Fig. 10–1)
• Estrogen—produced by follicle cells. Promotes
maturation of ovum; stimulates growth of blood
vessels in endometrium; stimulates development
of secondary sex characteristics: growth of duct
system of mammary glands, growth of uterus, fat
deposition. Promotes closure of epiphyses of
long bones; lowers blood levels of cholesterol
and triglycerides. Stimulus: FSH from anterior
pituitary.
• Progesterone—produced by the corpus luteum.
Promotes storage of glycogen and further
growth of blood vessels in the endometrium;
promotes growth of secretory cells of mammary
glands. Stimulus: LH from anterior pituitary.
• Inhibin—inhibits secretion of FSH.
Testes—in scrotum between the upper
thighs (see Fig. 10–1)
• Testosterone—produced by interstitial cells.
Promotes maturation of sperm in testes; stimulates
development of secondary sex characteristics:
growth of reproductive organs, facial and
body hair, larynx, skeletal muscles; promotes closure
of epiphyses of long bones. Stimulus: LH
from anterior pituitary.
• Inhibin—produced by sustentacular cells.
Inhibits secretion of FSH to maintain a constant
rate of sperm production. Stimulus: increased
testosterone.
Other Hormones
• Melatonin—secreted by the pineal gland during
darkness; brings on sleep.
• Prostaglandins—synthesized by cells from the
phospholipids of their cell membranes; exert
their effects locally. Are involved in inflammation
and pain, reproduction, nutrient metabolism,
changes in blood vessels, blood clotting.
Mechanisms of Hormone Action (see Fig.
10–12)
1. A hormone affects cells that have receptors for it.
Receptors are proteins that may be part of the cell
The Endocrine System 247
248 The Endocrine System
membrane, or within the cytoplasm or nucleus of
the target cell.
• The two-messenger mechanism: a protein hormone
(1st messenger) bonds to a membrane
receptor; stimulates formation of cyclic AMP
(2nd messenger), which activates the cell’s
enzymes to bring about the cell’s characteristic
response to the hormone.
• Steroid hormones diffuse easily through cell
membranes and bond to cytoplasmic receptors.
Steroid-protein complex enters the nucleus and
activates certain genes, which initiate protein
synthesis.
REVIEW QUESTIONS
1. Use the following to describe a negative feedback
mechanism: TSH, TRH, decreased metabolic rate,
thyroxine and T3. (p. 232)
2. Name the two hormones stored in the posterior
pituitary gland. Where are these hormones produced?
State the functions of each of these hormones.
(pp. 227–228)
3. Name the two hormones of the anterior pituitary
gland that affect the ovaries or testes, and state
their functions. (p. 230)
4. Describe the antagonistic effects of PTH and calcitonin
on bones and on blood calcium level. State
the other functions of PTH. (p. 233)
5. Describe the antagonistic effects of insulin and
glucagon on the liver and on blood glucose level.
(pp. 235–236)
6. Describe how cortisol affects the use of foods for
energy. Explain the anti-inflammatory effects of
cortisol. (pp. 240–241)
7. State the effect of aldosterone on the kidneys.
Describe the results of this effect on the composition
of the blood. (p. 240)
8. When are epinephrine and norepinephrine
secreted? Describe the effects of these hormones.
(p. 237)
9. Name the hormones necessary for development
of egg cells in the ovaries. Name the hormones
necessary for development of sperm in the testes.
(p. 243)
10. State what prostaglandins are made from. State
three functions of prostaglandins. (p. 244)
11. Name the hormones that promote the growth of
the endometrium of the uterus in preparation for
a fertilized egg, and state precisely where each
hormone is produced. (p. 243)
12. State the functions of thyroxine and T3. For what
aspects of growth are these hormones necessary?
(pp. 231–232)
13. Explain the functions of GH as they are related to
normal growth. (pp. 228–229)
14. State the direct stimulus for secretion of each of
these hormones: (pp. 227, 229, 232, 233, 235, 240,
241, 243)
a. Thyroxine
b. Insulin
c. Cortisol
d. PTH
e. Aldosterone
f. Calcitonin
g. GH
h. Glucagon
i. Progesterone
j. ADH
FOR FURTHER THOUGHT
1. During a soccer game, 12-year-old Alicia got in a
tangle with another player, fell hard on her hand,
and fractured her radius. She is going to be fine,
though she will be wearing a cast for a few weeks.
What hormones were secreted immediately after
the injury? What functions do they have? What
hormones will contribute to the healing of the
fracture, and how?
The Endocrine System 249
2. Darren is 15 years old, tall for his age, but he wants
to build more muscle. He decides that he will eat
only protein foods, because, he says, “Muscle is
protein, so protein will make protein, and the more
protein, the more muscle.” In part he is correct,
and in part incorrect. Explain, and name the hormones
involved in protein metabolism; state how
each affects protein metabolism.
3. Many people love pasta, others love potatoes, and
still others love rice. Name the hormones involved
in carbohydrate metabolism, and, for each, explain
its specific function.
4. Unfortunately, many fast-food meals are well
over 50% fat. Name the hormones involved in
fat metabolism, and, for each, explain its specific
function.
5. You have read about the liver several times in this
chapter, and often seen its picture as a target organ.
Many functions of the liver are stimulated by hormones.
Name as many hormones as you can think
of with effects on the liver, and state the function of
each.
250
CHAPTER 11
Chapter Outline
Characteristics of Blood
Plasma
Blood Cells
Red Blood Cells
Function
Production and maturation
Life span
Blood types
White Blood Cells
Classification
Functions
Platelets
Function
Prevention of abnormal clotting
BOX 11–1 ANEMIA
BOX 11–2 JAUNDICE
BOX 11–3 RH DISEASE OF THE NEWBORN
BOX 11–4 LEUKEMIA
BOX 11–5 WHITE BLOOD CELL TYPES: HLA
BOX 11–6 HEMOPHILIA
BOX 11–7 DISSOLVING CLOTS
Student Objectives
• Describe the composition and explain the functions
of blood plasma.
• Name the primary hemopoietic tissue and the
kinds of blood cells produced.
• State the function of red blood cells, including the
protein and the mineral involved.
• Name the nutrients necessary for red blood cell
production, and state the function of each.
• Explain how hypoxia may change the rate of red
blood cell production.
• Describe what happens to red blood cells that have
reached the end of their life span; what happens to
the hemoglobin?
• Explain the ABO and Rh blood types.
• Name the five kinds of white blood cells and
describe the function of each.
• State what platelets are, and explain how they are
involved in hemostasis.
• Describe the three stages of chemical blood clotting.
• Explain how abnormal clotting is prevented in the
vascular system.
• State the normal values in a complete blood count.
Blood
251
New Terminology
ABO group (A-B-O GROOP)
Albumin (al-BYOO-min)
Bilirubin (BILL-ee-roo-bin)
Chemical clotting (KEM-i-kuhl KLAH-ting)
Embolism (EM-boh-lizm)
Erythrocyte (e-RITH-roh-sight)
Hemoglobin (HEE-moh-GLOW-bin)
Hemostasis (HEE-moh-STAY-sis)
Heparin (HEP-ar-in)
Immunity (im-YOO-ni-tee)
Leukocyte (LOO-koh-sight)
Macrophage (MAK-roh-fahj)
Normoblast (NOR-moh-blast)
Reticulocyte (re-TIK-yoo-loh-sight)
Rh factor (R-H FAK-ter)
Thrombocyte (THROM-boh-sight)
Thrombus (THROM-bus)
Related Clinical Terminology
Anemia (uh-NEE-mee-yah)
Differential count (DIFF-er-EN-shul KOWNT)
Erythroblastosis fetalis (e-RITH-roh-blass-TOH-sis
fee-TAL-is)
Hematocrit (hee-MAT-oh-krit)
Hemophilia (HEE-moh-FILL-ee-ah)
Jaundice (JAWN-diss)
Leukemia (loo-KEE-mee-ah)
Leukocytosis (LOO-koh-sigh-TOH-sis)
RhoGAM (ROH-gam)
Tissue typing (TISH-yoo-TIGH-ping)
Typing and cross-matching (TIGH-ping and
KROSS-match-ing)
Terms that appear in bold type in the chapter text are defined in the glossary, which begins on page 547.
One of the simplest and most familiar life-saving
medical procedures is a blood transfusion. As you
know, however, the blood of one individual is not
always compatible with that of another person. The
ABO blood types were discovered in the early 1900s
by Karl Landsteiner, an Austrian-American. He
also contributed to the discovery of the Rh factor in
1940. In the early 1940s, Charles Drew, an African-
American, developed techniques for processing and
storing blood plasma, which could then be used in
transfusions for people with any blood type. When we
donate blood today, our blood may be given to a recipient
as whole blood, or it may be separated into its
component parts, and recipients will then receive only
those parts they need, such as red cells, plasma, factor
8, or platelets. Each of these parts has a specific function,
and all of the functions of blood are essential to
our survival.
The general functions of blood are transportation,
regulation, and protection. Materials transported by
the blood include nutrients, waste products, gases, and
hormones. The blood helps regulate fluid–electrolyte
balance, acid–base balance, and the body temperature.
Protection against pathogens is provided by white
blood cells, and the blood clotting mechanism prevents
excessive loss of blood after injuries. Each of these
functions is covered in more detail in this chapter.
CHARACTERISTICS OF BLOOD
Blood has distinctive physical characteristics:
Amount—a person has 4 to 6 liters of blood, depending
on his or her size. Of the total blood volume in
the human body, 38% to 48% is composed of the
various blood cells, also called formed elements. The
remaining 52% to 62% of the blood volume is
plasma, the liquid portion of blood (Fig. 11–1).
Color—you’re probably saying to yourself, “Of
course, it’s red!” Mention is made of this obvious
fact, however, because the color does vary. Arterial
blood is bright red because it contains high levels of
oxygen. Venous blood has given up much of its oxygen
in tissues, and has a darker, dull red color. This
may be important in the assessment of the source of
bleeding. If blood is bright red, it is probably from
a severed artery, and dark red blood is probably
venous blood.
pH—the normal pH range of blood is 7.35 to 7.45,
which is slightly alkaline. Venous blood normally
has a lower pH than does arterial blood because of
the presence of more carbon dioxide.
Viscosity—this means thickness or resistance to flow.
Blood is about three to five times thicker than
water. Viscosity is increased by the presence of
blood cells and the plasma proteins, and this thickness
contributes to normal blood pressure.
PLASMA
Plasma is the liquid part of blood and is approximately
91% water. The solvent ability of water
enables the plasma to transport many types of substances.
Nutrients absorbed in the digestive tract, such
as glucose, amino acids, and minerals, are circulated to
all body tissues. Waste products of the tissues, such as
urea and creatinine, circulate through the kidneys and
are excreted in urine. Hormones produced by
endocrine glands are carried in the plasma to their target
organs, and antibodies are also transported in
plasma. Most of the carbon dioxide produced by cells
is carried in the plasma in the form of bicarbonate ions
(HCO3
–). When the blood reaches the lungs, the CO2
is re-formed, diffuses into the alveoli, and is exhaled.
Also in the plasma are the plasma proteins. The
clotting factors prothrombin, fibrinogen, and others
are synthesized by the liver and circulate until activated
to form a clot in a ruptured or damaged blood
vessel. Albumin is the most abundant plasma protein.
It too is synthesized by the liver. Albumin contributes
to the colloid osmotic pressure of blood, which pulls
tissue fluid into capillaries. This is important to maintain
normal blood volume and blood pressure. Other
plasma proteins are called globulins. Alpha and beta
globulins are synthesized by the liver and act as carriers
for molecules such as fats. The gamma globulins
are antibodies produced by lymphocytes. Antibodies
initiate the destruction of pathogens and provide us
with immunity.
Plasma also carries body heat. Heat is one of the
by-products of cell respiration (the production of ATP
in cells). Blood is warmed by flowing through active
organs such as the liver and muscles. This heat is distributed
to cooler parts of the body as blood continues
to circulate.
252 Blood
253
Other body tissues and fluids 92% Blood
8%
Total body weight
Blood plasma 52–62% Blood cells 38–48% Blood volume
Water 91.5% Erythrocytes 4.5–6.0 million Blood cells
(per microliter)
Other substances
Other substances
1.5% 7%
Thrombocytes 150,000 – 300,000
Nutrients
Hormones
Nitrogenous
wastes
Respiratory
gases
Electrolytes
Fibrinogen 7%
Globulins
38%
Albumins
55%
Proteins
Basophils 0.5–1.0%
Eosinophils 1–3%
Monocytes 3–8%
Lymphocytes
20–35%
Neutrophils
55–70%
Proteins Leukocytes 5,000–10,000
Leukocytes
Figure 11–1. Components of blood and the relationship of blood to other body tissues.
QUESTION: Blood plasma is mostly what substance? Which blood cells are the most
numerous?
BLOOD CELLS
There are three kinds of blood cells: red blood cells,
white blood cells, and platelets. Blood cells are produced
from stem cells in hemopoietic tissue. After
birth this is primarily the red bone marrow, found
in flat and irregular bones such as the sternum,
hip bone, and vertebrae. Lymphocytes mature and
divide in lymphatic tissue, found in the spleen,
lymph nodes, and thymus gland. The thymus contains
stem cells that produce T lymphocytes, and the stem
cells in other lymphatic tissue also produce lymphocytes.
RED BLOOD CELLS
Also called erythrocytes, red blood cells (RBCs)
are biconcave discs, which means their centers are
thinner than their edges. You may recall from Chapter
3 that red blood cells are the only human cells without
nuclei. Their nuclei disintegrate as the red blood
cells mature and are not needed for normal functioning.
A normal RBC count ranges from 4.5 to 6.0 million
cells per microliter ( L) of blood (1 microliter 1
mm3 one millionth of a liter, a very small volume).
RBC counts for men are often toward the high end of
this range; those for women are often toward the low
end. Another way to measure the amount of RBCs is
the hematocrit. This test involves drawing blood into
a thin glass tube called a capillary tube, and centrifuging
the tube to force all the cells to one end. The percentages
of cells and plasma can then be determined.
Because RBCs are by far the most abundant of the
blood cells, a normal hematocrit range is just like that
of the total blood cells: 38% to 48%. Both RBC count
and hematocrit (Hct) are part of a complete blood
count (CBC).
Function
Red blood cells contain the protein hemoglobin
(Hb), which gives them the ability to carry oxygen.
Each red blood cell contains approximately 300 million
hemoglobin molecules, each of which can bond to
four oxygen molecules (see Box Fig. 3–B). In the pulmonary
capillaries, RBCs pick up oxygen and oxyhemoglobin
is formed. In the systemic capillaries,
hemoglobin gives up much of its oxygen and becomes
reduced hemoglobin. A determination of hemoglobin
level is also part of a CBC; the normal range is 12 to
18 grams per 100 mL of blood. Essential to the formation
of hemoglobin is the mineral iron; there are
four atoms of iron in each molecule of hemoglobin. It
is the iron that actually bonds to the oxygen and also
makes RBCs red.
Hemoglobin is also able to bond to carbon dioxide
(CO2), and does transport some CO2 from the tissues
to the lungs. But hemoglobin accounts for only about
10% of total CO2 transport (most is carried in the
plasma as bicarbonate ions).
Production and Maturation
Red blood cells are formed in red bone marrow (RBM)
in flat and irregular bones. Within red bone marrow
are precursor cells called stem cells. Recall from
Chapter 3 that stem cells are unspecialized cells that
may develop, or differentiate, in several ways. The
stem cells of the red bone marrow may also be called
hemocytoblasts (hemo “blood,” cyto “cell,” blast
“producing”), and they constantly undergo mitosis
to produce all the kinds of blood cells, many of which
are RBCs (Figs. 11–2 and 11–3). The rate of production
is very rapid (estimated at several million new
RBCs per second), and a major regulating factor is
oxygen. If the body is in a state of hypoxia, or lack of
oxygen, the kidneys produce a hormone called erythropoietin,
which stimulates the red bone marrow to
increase the rate of RBC production (that is, the rate
of stem cell mitosis). This will occur following hemorrhage
or if a person stays for a time at a higher altitude.
As a result of the action of erythropoietin, more RBCs
will be available to carry oxygen and correct the
hypoxic state.
The stem cells that will become RBCs go through
a number of developmental stages, only the last two of
which we will mention (see Fig. 11–2). The normoblast
is the last stage with a nucleus, which then
disintegrates. The reticulocyte has fragments of the
endoplasmic reticulum, which are visible when blood
smears are stained for microscopic evaluation. These
immature cells are usually found in the red bone marrow,
although a small number of reticulocytes in the
peripheral circulation is considered normal (up to
1.5% of the total RBCs). Large numbers of reticulocytes
or normoblasts in the circulating blood mean
that the number of mature RBCs is not sufficient to
254 Blood
255
Macrophage
Plasma cell
T cell
Monocyte
Thrombocytes
(platelets)
Stem cell Lymphoblast
B cell
Natural
killer
cell
Eosinophil
Megakaryocyte
Normoblasts
Reticulocytes
Erythrocytes
Basophil
Neutrophil
Band cell
Figure 11–2. Production of blood cells. Stem cells are found primarily in red bone marrow
and are the precursor cells for all the types of blood cells.
QUESTION: Where are normoblasts and reticulocytes usually found, and why?
carry the oxygen needed by the body. Such situations
include hemorrhage, or when mature RBCs have
been destroyed, as in Rh disease of the newborn, and
malaria.
The maturation of red blood cells requires many
nutrients. Protein and iron are necessary for the synthesis
of hemoglobin and become part of hemoglobin
molecules. Copper is part of some enzymes involved
in hemoglobin synthesis. The vitamins folic acid and
B12 are required for DNA synthesis in the stem cells of
the red bone marrow. As these cells undergo mitosis,
they must continually produce new sets of chromosomes.
Vitamin B12 is also called the extrinsic factor
because its source is external, our food. Parietal cells
of the stomach lining produce the intrinsic factor, a
chemical that combines with the vitamin B12 in food to
prevent its digestion and promote its absorption in the
small intestine. A deficiency of either vitamin B12 or
the intrinsic factor results in pernicious anemia
(see Box 11–1: Anemia).
Life Span
Red blood cells live for approximately 120 days.
As they reach this age they become fragile and are
removed from circulation by cells of the tissue
macrophage system (formerly called the reticuloendothelial
or RE system). The organs that contain
macrophages (literally, “big eaters”) are the liver,
spleen, and red bone marrow. Look at Fig. 11–4 as you
read the following. The old RBCs are phagocytized
and digested by macrophages, and the iron they contained
is put into the blood to be returned to the red
bone marrow to be used for the synthesis of new
hemoglobin. If not needed immediately for this purpose,
excess iron is stored in the liver. The iron of
256 Blood
Figure 11–3. Blood cells.
(A) Red blood cells, platelets, and a
basophil. (B) Lymphocyte (left) and
neutrophil (right). (C) Eosinophil.
(D) Monocytes. (E) Megakaryocyte
with platelets. (A–E 600)
(F) Normal bone marrow ( 200).
(From Harmening, DM: Clinical
Hematology and Fundamentals
of Hemostasis, ed. 3. FA Davis,
Philadelphia, 1997, pp 14, 17, 19,
26, 48, with permission.)
QUESTION: Look at the RBCs in
picture B. Why do they have pale
centers?
A B
D
E F
C
Blood 257
BOX 11–1 ANEMIA
Aplastic anemia is suppression of the red bone
marrow, with decreased production of RBCs, WBCs,
and platelets. This is a very serious disorder that
may be caused by exposure to radiation, certain
chemicals such as benzene, or some medications.
There are several antibiotics that must be used with
caution since they may have this potentially fatal
side effect.
Hemolytic anemia is any disorder that causes
rupture of RBCs before the end of their normal life
span. Sickle-cell anemia and Rh disease of the newborn
are examples. Another example is malaria, in
which a protozoan parasite reproduces in RBCs and
destroys them. Hemolytic anemias are often characterized
by jaundice because of the increased production
of bilirubin.
Anemia is a deficiency of red blood cells, or insufficient
hemoglobin within the red blood cells. There
are many different types of anemia.
Iron-deficiency anemia is caused by a lack of
dietary iron, and there is not enough of this mineral
to form sufficient hemoglobin. A person with this
type of anemia may have a normal RBC count and
a normal hematocrit, but the hemoglobin level will
be below normal.
A deficiency of vitamin B12, which is found only
in animal foods, leads to pernicious anemia, in
which the RBCs are large, misshapen, and fragile.
Another cause of this form of anemia is lack of the
intrinsic factor due to autoimmune destruction of
the parietal cells of the stomach lining.
Sickle-cell anemia has already been discussed
in Chapter 3. It is a genetic disorder of hemoglobin,
which causes RBCs to sickle, clog capillaries, and
rupture.
A B
C D
Box Figure 11–A Anemia. (A) Iron-deficiency anemia; notice the pale, oval RBCs ( 400).
(B) Pernicious anemia, with large, misshapen RBCs ( 400). (C) Sickle-cell anemia ( 400).
(D) Aplastic anemia, bone marrow ( 200). (A, B, and C from Listen, Look, and Learn, Vol
3; Coagulation, Hematology. The American Society of Clinical Pathologists Press, Chicago,
1973, with permission. D from Harmening, DM: Clinical Hematology and Fundamentals of
Hemostasis, ed 3. FA Davis, Philadelphia, 1997, p 49, with permission.)
RBCs is actually recycled over and over again. The
globin or protein portion of the hemoglobin molecule
is also recycled. It is digested to its amino acids, which
may then be used for the synthesis of new proteins.
Another part of the hemoglobin molecule is the
heme portion, which cannot be recycled and is a waste
product. The heme is converted to bilirubin by
macrophages. The liver removes bilirubin from circulation
and excretes it into bile; bilirubin is a bile pigment.
Bile is secreted by the liver into the duodenum
and passes through the small intestine and colon, so
bilirubin is eliminated in feces, and gives feces their
characteristic brown color. In the colon some bilirubin
is changed to urobilinogen by the colon bacteria.
258 Blood
New RBCs
formed in
red bone marrow
Used to make
new RBCs
Iron Heme Globin
Stored in
liver
Bilirubin
Small
intestine
Large intestine
Bilirubin
Colon
bacteria
Urobilin
Urobilin
Urine
Amino acids
Protein synthesis
Macrophages in
liver, spleen, and
red bone marrow
phagocytize old RBCs
Kidney
RBCs Circulate
120 days
Figure 11–4. Life cycle of red blood cells. See text for description.
QUESTION: Which components of old RBCs are recycled? Which is excreted? (Go to the
macrophage and follow the arrows.)
Some urobilinogen may be absorbed into the blood,
but it is changed to urobilin and excreted by the kidneys
in urine. If bilirubin is not excreted properly, perhaps
because of liver disease such as hepatitis, it
remains in the blood. This may cause jaundice, a condition
in which the whites of the eyes appear yellow.
This yellow color may also be seen in the skin of lightskinned
people (see Box 11–2: Jaundice).
Blood Types
Our blood types are genetic; that is, we inherit genes
from our parents that determine our own types. There
are many red blood cell factors or types; we will discuss
the two most important ones: the ABO group
and the Rh factor. (The genetics of blood types is discussed
in Chapter 21.)
The ABO group contains four blood types: A, B,
AB, and O. The letters A and B represent antigens
(protein-oligosaccharides) on the red blood cell membrane.
A person with type A blood has the A antigen
on the RBCs, and someone with type B blood has the
B antigen. Type AB means that both A and B antigens
are present, and type O means that neither the A nor
the B antigen is present.
Circulating in the plasma of each person are natural
antibodies for those antigens not present on the
RBCs. Therefore, a type A person has anti-B antibodies
in the plasma; a type B person has anti-A antibodies;
a type AB person has neither anti-A nor anti-B
antibodies; and a type O person has both anti-A and
anti-B antibodies (see Table 11–1 and Fig. 11–5).
These natural antibodies are of great importance
for transfusions. If possible, a person should receive
Blood 259
BOX 11–2 JAUNDICE
born; these are hemolytic anemias. As excessive
numbers of RBCs are destroyed, bilirubin is formed
at a faster rate than the liver can excrete it. The
bilirubin that the liver cannot excrete remains in the
blood and causes jaundice. Another name for this
type is hemolytic jaundice.
Posthepatic jaundice means that the problem
is “after” the liver. The liver excretes bilirubin into
bile, which is stored in the gallbladder and then
moved to the small intestine. If the bile ducts are
obstructed, perhaps by gallstones or inflammation
of the gallbladder, bile cannot pass to the small
intestine and backs up in the liver. Bilirubin may
then be reabsorbed back into the blood and cause
jaundice. Another name for this type is obstructive
jaundice.
Jaundice is not a disease, but rather a sign caused
by excessive accumulation of bilirubin in the blood.
Because one of the liver’s many functions is the
excretion of bilirubin, jaundice may be a sign of
liver disease such as hepatitis or cirrhosis. This may
be called hepatic jaundice, because the problem
is with the liver.
Other types of jaundice are prehepatic jaundice
and posthepatic jaundice: The name of each tells us
where the problem is. Recall that bilirubin is the
waste product formed from the heme portion of
the hemoglobin of old RBCs. Prehepatic jaundice
means that the problem is “before” the liver;
that is, hemolysis of RBCs is taking place at a more
rapid rate. Rapid hemolysis is characteristic of sicklecell
anemia, malaria, and Rh disease of the new-
Table 11–1 ABO BLOOD TYPES
Antigens Present Antibodies Present Percentage in U.S. Population*
Type on RBCs in Plasma White Black Asian
A A anti-B 40 27 31
B B anti-A 11 20 26
AB both A and B neither anti-A nor anti-B 4 4 8
O neither A nor B both anti-A and anti-B 45 49 35
*Average.
260
Type A
Type
AB
Red blood cells Plasma Anti-A serum Anti-B serum
ABO blood types Typing and cross-matching
Type A
Type B Type B
Type AB Type AB
Type O Type O
A antigens B antibodies
B antigens A antibodies
A and B antigens Neither A nor B antibodies
Neither A
nor B antigens
A and B antibodies
Type
O
Type
A
Type
A
Type
O
Type
B
Type
B
Universal donor
Type
AB
Universal recipient
A B
C
Figure 11–5. (A) The ABO blood types. Schematic representation of antigens on the
RBCs and antibodies in the plasma. (B) Typing and cross-matching. The A or B antiserum
causes agglutination of RBCs with the matching antigen. (C) Acceptable transfusions are
diagrammed and presuppose compatible Rh factors.
QUESTION: In part C, find your blood type. To whom (that is, to which blood types) can
you donate blood?
blood of his or her own type; only if this type is not
available should another type be given. For example,
let us say that a type A person needs a transfusion to
replace blood lost in hemorrhage. If this person were
to receive type B blood, what would happen? The type
A recipient has anti-B antibodies that would bind to
the type B antigens of the RBCs of the donated blood.
The type B RBCs would first clump (agglutination)
then rupture (hemolysis), thus defeating the purpose
of the transfusion. An even more serious consequence
is that the hemoglobin of the ruptured RBCs, now
called free hemoglobin, may clog the capillaries of the
kidneys and lead to renal damage or renal failure. You
can see why typing and cross-matching of donor and
recipient blood in the hospital laboratory is so important
before any transfusion is given (see Fig. 11–5).
This procedure helps ensure that donated blood will
not bring about a hemolytic transfusion reaction in
the recipient.
You may have heard of the concept that a person
with type O blood is a “universal donor.” Usually, a
unit of type O negative blood may be given to people
with any other blood type. This is so because type O
RBCs have neither the A nor the B antigens and will
not react with whatever antibodies the recipient may
have. If only one unit (1 pint) of blood is given, the
anti-A and anti-B antibodies in the type O blood
plasma will be diluted in the recipient’s blood plasma
and will not have a harmful effect on the recipient’s
RBCs. The term negative, in O negative, the universal
donor, refers to the Rh factor, which we will now
consider.
The Rh factor is another antigen (often called D)
that may be present on RBCs. People whose RBCs
have the Rh antigen are Rh positive; those without
the antigen are Rh negative. Rh-negative people do
not have natural antibodies to the Rh antigen, and
for them this antigen is foreign. If an Rh-negative
person receives Rh-positive blood by mistake,
antibodies will be formed just as they would be
to bacteria or viruses. A first mistaken transfusion
often does not cause problems, because antibody production
is slow upon the first exposure to Rh-positive
RBCs. A second transfusion, however, when anti-Rh
antibodies are already present, will bring about a
transfusion reaction, with hemolysis and possible kidney
damage (see also Box 11–3: Rh Disease of the
Newborn).
WHITE BLOOD CELLS
White blood cells (WBCs) are also called leukocytes.
There are five kinds of WBCs; all are larger than
RBCs and have nuclei when mature. The nucleus may
be in one piece or appear as several lobes or segments.
Special staining for microscopic examination gives
each kind of WBC a distinctive appearance (see Figs.
11–2 and 11–3).
Blood 261
BOX 11–3 Rh DISEASE OF THE NEWBORN
baby will be born anemic and jaundiced from the
loss of RBCs. Such an infant may require a gradual
exchange transfusion to remove the blood with the
maternal antibodies and replace it with Rh-negative
blood. The baby will continue to produce its own
Rh-positive RBCs, which will not be destroyed once
the maternal antibodies have been removed.
Much better than treatment, however, is prevention.
If an Rh-negative woman delivers an Rhpositive
baby, she should be given RhoGAM within
72 hours after delivery. RhoGAM is an anti-Rh antibody
that will destroy any fetal RBCs that have
entered the mother’s circulation before her immune
system can respond and produce antibodies. The
RhoGAM antibodies themselves break down within
a few months. The woman’s next pregnancy will be
like the first, as if she had never been exposed to
Rh-positive RBCs.
Rh disease of the newborn may also be called
erythroblastosis fetalis and is the result of an Rh
incompatibility between mother and fetus. During
a normal pregnancy, maternal blood and fetal
blood do not mix in the placenta. However, during
delivery of the placenta (the “afterbirth” that follows
the birth of the baby), some fetal blood may
enter maternal circulation.
If the woman is Rh negative and her baby is Rh
positive, this exposes the woman to Rh-positive
RBCs. In response, her immune system will now
produce anti-Rh antibodies following this first delivery.
In a subsequent pregnancy, these maternal
antibodies will cross the placenta and enter fetal circulation.
If this next fetus is also Rh positive, the
maternal antibodies will cause destruction (hemolysis)
of the fetal RBCs. In severe cases this may result
in the death of the fetus. In less severe cases, the
A normal WBC count (part of a CBC) is 5,000 to
10,000 per L. Notice that this number is quite small
compared to a normal RBC count. Many of our
WBCs are not circulating within blood vessels but are
carrying out their functions in tissue fluid or in lymphatic
tissue.
Classification
The five kinds of white blood cells, all produced in the
red bone marrow (and some lymphocytes in lymphatic
tissue), may be classified in two groups: granular and
agranular. The granular leukocytes are the neutrophils,
eosinophils, and basophils, which usually
have nuclei in two or more lobes or segments, and
have distinctly colored granules when stained.
Neutrophils have light blue granules, eosinophils have
red granules, and basophils have dark blue granules.
The agranular leukocytes are lymphocytes and
monocytes, which have nuclei in one piece.
Monocytes are usually quite a bit larger than lymphocytes.
A differential WBC count (part of a CBC) is
the percentage of each kind of leukocyte. Normal
ranges are listed in Table 11–2, along with other normal
values of a CBC.
Functions
White blood cells all contribute to the same general
function, which is to protect the body from infectious
disease and to provide immunity to certain diseases.
Each kind of leukocyte makes a contribution to this
very important aspect of homeostasis.
Neutrophils and monocytes are capable of the
phagocytosis of pathogens. Neutrophils are the more
abundant phagocytes, but the monocytes are the more
efficient phagocytes, because they differentiate into
macrophages, which also phagocytize dead or damaged
tissue at the site of any injury, helping to make
tissue repair possible. During an infection, neutrophils
are produced more rapidly, and the immature forms,
called band cells (see Fig. 11–2), may appear in
greater numbers in peripheral circulation (band cells
are usually less than 10% of the total neutrophils).
The term “band” refers to the nucleus that has not yet
become segmented, and may look somewhat like a
dumbbell.
Eosinophils are believed to detoxify foreign
proteins and will phagocytize anything labeled with
antibodies. This is especially important in allergic
reactions and parasitic infections such as trichinosis (a
worm parasite). Basophils contain granules of heparin
and histamine. Heparin is an anticoagulant that helps
prevent abnormal clotting within blood vessels.
Histamine, you may recall, is released as part of the
inflammation process, and it makes capillaries more
permeable, allowing tissue fluid, proteins, and white
blood cells to accumulate in the damaged area.
There are two major kinds of lymphocytes, T cells
and B cells, and a less numerous third kind called natural
killer cells. For now we will say that T cells (or T
lymphocytes) help recognize foreign antigens and may
directly destroy some foreign antigens. B cells (or B
lymphocytes) become plasma cells that produce antibodies
to foreign antigens. Both T cells and B cells
provide memory for immunity. Natural killer cells
(NK cells) destroy foreign cells by chemically rupturing
their membranes. These functions of lymphocytes
are discussed in the context of the mechanisms of
immunity in Chapter 14.
As mentioned earlier, leukocytes function in tissue
fluid as well as in the blood. Many WBCs are capable
of self-locomotion (ameboid movement) and are able
to squeeze between the cells of capillary walls and out
into tissue spaces. Macrophages provide a good example
of the dual locations of leukocytes. Some
macrophages are “fixed,” that is, stationary in organs
such as the liver, spleen, and red bone marrow (part of
the tissue macrophage or RE system—the same
262 Blood
Table 11–2 COMPLETE BLOOD COUNT
Measurement Normal Range*
Red blood cells
Hemoglobin
Hematocrit
Reticulocytes
White blood cells (total)
Neutrophils
Eosinophils
Basophils
Lymphocytes
Monocytes
Platelets
*The values on hospital lab slips may vary somewhat but
will be very similar to the normal ranges given here.
• 4.5–6.0 million/ L
• 12–18 grams/100 mL
• 38%–48%
• 0%–1.5%
• 5000–10,000/ L
• 55%–70%
• 1%–3%
• 0.5%–1%
• 20%–35%
• 3%–8%
• 150,000–300,000/ L
macrophages that phagocytize old RBCs) and in the
lymph nodes. They phagocytize pathogens that circulate
in blood or lymph through these organs. Other
“wandering” macrophages move about in tissue fluid,
especially in the areolar connective tissue of mucous
membranes and below the skin. Pathogens that gain
entry into the body through natural openings or
through breaks in the skin are usually destroyed by the
macrophages and other leukocytes in connective tissue
before they can cause serious disease. The alveoli
of the lungs, for example, have macrophages that
very efficiently destroy pathogens that enter with
inhaled air.
A high WBC count, called leukocytosis, is often
an indication of infection. Leukopenia is a low WBC
count, which may be present in the early stages of diseases
such as tuberculosis. Exposure to radiation or to
chemicals such as benzene may destroy WBCs and
lower the total count. Such a person is then very susceptible
to infection. Leukemia, or malignancy of
leukocyte-forming tissues, is discussed in Box 11–4:
Leukemia.
The white blood cell types (analogous to RBC types
such as the ABO group) are called human leukocyte
antigens (HLA) and are discussed in Box 11–5: White
Blood Cell Types: HLA.
PLATELETS
The more formal name for platelets is thrombocytes,
which are not whole cells but rather fragments or
pieces of cells. Some of the stem cells in the red bone
marrow differentiate into large cells called megakaryocytes
(see Figs. 11–2 and 11–3), which break up into
small pieces that enter circulation. These small, oval,
circulating pieces are platelets, which may last for 5 to
9 days, if not utilized before that. Thrombopoietin is
a hormone produced by the liver that increases the
rate of platelet production.
A normal platelet count (part of a CBC) is 150,000
to 300,000/ L (the high end of the range may be
extended to 500,000). Thrombocytopenia is the term
for a low platelet count.
Function
Platelets are necessary for hemostasis, which means
prevention of blood loss. There are three mechanisms,
Blood 263
BOX 11–4 LEUKEMIA
Chemotherapy may bring about cure or remission
for some forms of leukemia, but other forms
remain resistant to treatment and may be fatal
within a few months of diagnosis. In such cases, the
cause of death is often pneumonia or some other
serious infection, because the abnormal white
blood cells cannot prevent the growth and spread
of pathogens within the body.
Leukemia is the term for malignancy of the bloodforming
tissue. There are many types of leukemia,
which are classified as acute or chronic, by the
types of abnormal cells produced, and by either
childhood or adult onset.
In general, leukemia is characterized by an overproduction
of immature white blood cells. These
immature cells cannot perform their normal functions,
and the person becomes very susceptible to
infection. As a greater proportion of the body’s
nutrients are used by malignant cells, the production
of other blood cells decreases. Severe anemia is
a consequence of decreased red blood cell production,
and the tendency to hemorrhage is the result
of decreased platelets.
Box Figure 11–B Leukemia. Notice the many
darkly staining WBCs ( 300). (From Sacher, RA, and
McPherson, RA: Widmann’s Clinical Interpretation
of Laboratory Tests, ed 11. FA Davis, Philadelphia,
2000, with permission.)
and platelets are involved in each. Two of these mechanisms
are shown in Fig. 11–6.
1. Vascular spasm—when a large vessel such as an
artery or vein is severed, the smooth muscle in its
wall contracts in response to the damage (called the
myogenic response). Platelets in the area of the
rupture release serotonin, which also brings about
vasoconstriction. The diameter of the vessel is
thereby made smaller, and the smaller opening may
then be blocked by a blood clot. If the vessel did
not constrict first, the clot that forms would quickly
be washed out by the force of the blood pressure.
2. Platelet plugs—when capillaries rupture, the
damage is too slight to initiate the formation of a
blood clot. The rough surface, however, causes
platelets to change shape (become spiky) and
become sticky. These activated platelets stick to the
edges of the break and to each other. The platelets
form a mechanical barrier or wall to close off the
break in the capillary. Capillary ruptures are quite
frequent, and platelet plugs, although small, are all
that is needed to seal them.
Would platelet plugs be effective for breaks in
larger vessels? No, they are too small, and though
they do form, they are washed away (until a clot
begins to form that can contain them). Would vascular
spasm be effective for capillaries? Again, the
answer is no, because capillaries have no smooth
muscle and cannot constrict at all.
264 Blood
BOX 11–5 WHITE BLOOD CELL TYPES: HLA
the HLA types of a donated organ to see if one or
several will match the HLA types of the potential
recipient. If even one HLA type matches, the chance
of rejection is lessened. Although all transplant
recipients (except corneal) must receive immunosuppressive
medications to prevent rejection, such
medications make them more susceptible to infection.
The closer the HLA match of the donated
organ, the lower the dosage of such medications,
and the less chance of serious infections. (The
chance of finding a perfect HLA match in the general
population is estimated at 1 in 20,000.)
There is yet another aspect of the importance of
HLA: People with certain HLA types seem to be
more likely to develop certain non-infectious diseases.
For example, type 1 (insulin-dependent) diabetes
mellitus is often found in people with HLA
DR3 or DR4, and a form of arthritis of the spine
called ankylosing spondylitis is often found in those
with HLA B27. These are not genes for these diseases,
but may be predisposing factors. What may
happen is this: A virus enters the body and stimulates
the immune system to produce antibodies.
The virus is destroyed, but one of the person’s own
antigens is so similar to the viral antigen that the
immune system continues its activity and begins to
destroy this similar part of the body. Another possibility
is that a virus damages a self-antigen to the
extent that it is now so different that it will be perceived
as foreign. These are two theories of how
autoimmune diseases are triggered, which is the
focus of much research in the field of immunology.
Human leukocyte antigens (HLA) are antigens
on WBCs that are representative of the antigens
present on all the cells of an individual. These are
our “self” antigens that identify cells that belong in
the body.
Recall that in the ABO blood group of RBCs,
there are only two antigens, A and B, and four
possible types: A, B, AB, and O. HLA antigens are
also given letter names. HLA A, B, and C are called
class I proteins, with from 100 to more than 400
possibilities for the specific protein each can be. The
several class II proteins are given various D designations
and, again, there are many possibilities for
each. Each person has two genes for each HLA type,
because these types are inherited, just as RBC types
are inherited. Members of the same family may
have some of the same HLA types, and identical
twins have exactly the same HLA types.
The purpose of the HLA types is to provide a
“self” comparison for the immune system to use
when pathogens enter the body. The T lymphocytes
compare the “self” antigens on macrophages
to the antigens on bacteria and viruses. Because
these antigens do not match ours, they are recognized
as foreign; this is the first step in the destruction
of a pathogen.
The surgical transplantation of organs has also
focused on the HLA. The most serious problem for
the recipient of a transplanted heart or kidney is
rejection of the organ and its destruction by the
immune system. You may be familiar with the term
tissue typing. This process involves determining
3. Chemical clotting—The stimulus for clotting is a
rough surface within a vessel, or a break in the vessel,
which also creates a rough surface. The more
damage there is, the faster clotting begins, usually
within 15 to 120 seconds.
The clotting mechanism is a series of reactions
involving chemicals that normally circulate in the
blood and others that are released when a vessel is
damaged.
The chemicals involved in clotting include platelet
factors, chemicals released by damaged tissues, calcium
ions, and the plasma proteins prothrombin, fibrinogen,
Factor 8, and others synthesized by the liver.
(These clotting factors are also designated by Roman
numerals; Factor 8 would be Factor VIII.) Vitamin K
is necessary for the liver to synthesize prothrombin
and several other clotting factors (Factors 7, 9, and 10).
Most of our vitamin K is produced by the bacteria that
live in the colon; the vitamin is absorbed as the colon
absorbs water and may be stored in the liver.
Chemical clotting is usually described in three
stages, which are listed in Table 11–3 and illustrated in
Fig. 11–7. Stage 1 begins when a vessel is cut or damaged
internally, and includes all of the factors shown.
As you follow the pathway, notice that the product of
stage 1 is prothrombin activator, which may also be
called prothrombinase. Each name tells us something.
The first name suggests that this chemical activates
prothrombin, and that is true. The second name ends
in “ase,” which indicates that this is an enzyme. The
traditional names for enzymes use the substrate of the
enzyme as the first part of the name, and add “ase.” So
this chemical must be an enzyme whose substrate is
Blood 265
Skin is cut and
blood escapes from a
capillary and an
arteriole.
Capillary
Arteriole
Platelets
Fibrin
In the capillary, platelets
stick to the ruptured wall
and form a platelet plug.
In the arteriole, chemical
clotting forms a fibrin clot.
Clot retraction pulls the
edges of the break together.
Figure 11–6. Hemostasis. Platelet
plug formation in a capillary and
chemical clotting and clot retraction
in an arteriole.
QUESTION: Look at the diameter of
the arteriole (compared to that of
the capillary) and explain why
platelet plugs would not be sufficient
to stop the bleeding.
prothrombin, and that is also true. The stages of clotting
may be called a cascade, where one leads to the
next, as inevitable as water flowing downhill. Prothrombin
activator, the product of stage 1, brings
about the stage 2 reaction: converting prothrombin to
thrombin. The product of stage 2, thrombin, brings
about the stage 3 reaction: converting fibrinogen to
fibrin (see Box 11–6: Hemophilia).
The clot itself is made of fibrin, the product of
stage 3. Fibrin is a thread-like protein. Many strands
of fibrin form a mesh that traps RBCs and platelets,
and creates a wall across the break in the vessel.
Once the clot has formed and bleeding has stopped,
clot retraction and fibrinolysis occur. Clot retraction
requires platelets, ATP, and Factor 13 and involves
folding of the fibrin threads to pull the edges of the
rupture in the vessel wall closer together. This will
make the area to be repaired smaller. The platelets
contribute in yet another way, because as they disintegrate
they release platelet-derived growth factor
(PDGF), which stimulates the repair of blood vessels
(growth of their tissues). As repair begins, the clot is
dissolved, a process called fibrinolysis. It is important
that the clot be dissolved, because it is a rough surface,
266 Blood
Table 11–3 CHEMICAL CLOTTING
Clotting Stage Factors Needed Reaction
Stage 1
Stage 2
Stage 3
• Platelet factors
• Chemicals from damaged tissue
(tissue thromboplastin)
• Factors 5,7,8,9,10,11,12
• Calcium ions
• Prothrombin activator from stage 1
• Prothrombin
• Calcium ions
• Thrombin from stage 2
• Fibrinogen
• Calcium ions
• Factor 13 (fibrin stabilizing factor)
Platelet factors tissue thromboplastin
other clotting factors calcium ions
form prothrombin activator
Prothrombin activator converts prothrombin
to thrombin
Thrombin converts fibrinogen to fibrin
BOX 11–6 HEMOPHILIA
cure) has become possible with factor 8 obtained
from blood donors. The Factor 8 is extracted from
the plasma of donated blood and administered in
concentrated form to hemophiliacs, enabling them
to live normal lives.
In what is perhaps the most tragic irony of medical
progress, many hemophiliacs were inadvertently
infected with HIV, the virus that causes AIDS.
Before 1985, there was no test to detect HIV in
donated blood, and the virus was passed to hemophiliacs
in the very blood product that was meant
to control their disease and prolong their lives.
Today, all donated blood and blood products are
tested for HIV, and the risk of AIDS transmission to
hemophiliacs, or anyone receiving donated blood,
is now very small.
There are several forms of hemophilia; all are
genetic and are characterized by the inability of
the blood to clot properly. Hemophilia A is the
most common form and involves a deficiency of
clotting Factor 8. The gene for hemophilia A is
located on the X chromosome, so this is a sexlinked
trait, with the same pattern of inheritance
as red-green color blindness and Duchenne’s muscular
dystrophy.
Without factor 8, the first stage of chemical
clotting cannot be completed, and prothrombin
activator is not formed. Without treatment, a
hemophiliac experiences prolonged bleeding after
even minor injuries and extensive internal bleeding,
especially in joints subjected to the stresses of
weight-bearing. In recent years, treatment (but not
Blood 267
Factors 5, 7, 8, 9,
10, 11, 12
Platelet factors
Chemicals from
damaged tissue Calcium
ions
Prothrombin
activator
Prothrombin
Calcium
ions
Thrombin
Fibrinogen
Calcium ions
Factor 13
Fibrin
Stage 1
Stage 2
Stage 3
Liver
Figure 11–7. Stages of chemical blood clotting.
QUESTION: Based only on this picture, explain why the liver is a vital organ.
and if it were inside a vessel it would stimulate more
and unnecessary clotting, which might eventually
obstruct blood flow.
Prevention of Abnormal Clotting
Clotting should take place to stop bleeding, but too
much clotting would obstruct vessels and interfere
with normal circulation of blood. Clots do not usually
form in intact vessels because the endothelium (simple
squamous epithelial lining) is very smooth and
repels the platelets and clotting factors. If the lining
becomes roughened, as happens with the lipid deposits
of atherosclerosis, a clot will form.
Heparin, produced by basophils, is a natural anticoagulant
that inhibits the clotting process (although
heparin is called a “blood thinner,” it does not “thin”
or dilute the blood in any way; rather it prevents a
chemical reaction from taking place). The liver produces
a globulin called antithrombin, which combines
with and inactivates excess thrombin. Excess thrombin
would exert a positive feedback effect on the clotting
cascade, and result in the splitting of more prothrombin
to thrombin, more clotting, more thrombin
formed, and so on. Antithrombin helps to prevent this,
as does the fibrin of the clot, which adsorbs excess
thrombin and renders it inactive. All of these factors
are the external brake for this positive feedback mechanism.
Together they usually limit the fibrin formed to
what is needed to create a useful clot but not an
obstructive one.
Thrombosis refers to clotting in an intact vessel;
the clot itself is called a thrombus. Coronary thrombosis,
for example, is abnormal clotting in a coronary
artery, which will decrease the blood (oxygen) supply
to part of the heart muscle. An embolism is a clot
or other tissue transported from elsewhere that lodges
in and obstructs a vessel (see Box 11–7: Dissolving
Clots).
SUMMARY
All of the functions of blood described in this chapter—
transport, regulation, and protection—contribute
to the homeostasis of the body as a whole.
However, these functions could not be carried out if
the blood did not circulate properly. The circulation
of blood throughout the blood vessels depends upon
the proper functioning of the heart, the pump of the
circulatory system, which is the subject of our next
chapter.
268 Blood
BOX 11–7 DISSOLVING CLOTS
Abnormal clots may cause serious problems in
coronary arteries, pulmonary arteries, cerebral
vessels, and even veins in the legs. However, if
clots can be dissolved before they cause death of
tissue, normal circulation and tissue functioning
may be restored.
One of the first substances used to dissolve
clots in coronary arteries was streptokinase,
which is actually a bacterial toxin produced
by some members of the genus Streptococcus.
Streptokinase did indeed dissolve clots, but its
use created the possibility of clot destruction
throughout the body, with serious hemorrhage a
potential consequence.
Safer chemicals called third-generation
thrombolytics are now used (thrombo “clot”
and lytic “to lyse” or “split”). In a case of coronary
thrombosis, if a thrombolytic can be administered
within a few hours, the clot may be
dissolved and permanent heart damage prevented.
The same procedure is also used to prevent
permanent brain damage after strokes
(CVAs) caused by blood clots.
STUDY OUTLINE
The general functions of blood are transportation,
regulation, and protection.
Characteristics of Blood
1. Amount—4 to 6 liters; 38% to 48% is cells; 52% to
62% is plasma (Fig. 11–1).
2. Color—arterial blood has a high oxygen content
and is bright red; venous blood has less oxygen and
is dark red.
3. pH—7.35 to 7.45; venous blood has more CO2 and
a lower pH than arterial blood.
4. Viscosity—thickness or resistance to flow; due to
the presence of cells and plasma proteins; contributes
to normal blood pressure.
Plasma—the liquid portion of blood
1. 91% water.
2. Plasma transports nutrients, wastes, hormones,
antibodies, and CO2 as HCO3
–.
3. Plasma proteins: clotting factors are synthesized by
the liver; albumin is synthesized by the liver and
provides colloid osmotic pressure that pulls tissue
fluid into capillaries to maintain normal blood volume
and blood pressure; alpha and beta globulins
are synthesized by the liver and are carriers for fats
and other substances in the blood; gamma globulins
are antibodies produced by lymphocytes.
Blood Cells
1. Formed elements are RBCs, WBCs, and platelets
(Figs. 11–2 and 11–3).
2. After birth the primary hemopoietic tissue is the
red bone marrow, which contains stem cells.
Lymphocytes mature and divide in the lymphatic
tissue of the spleen, lymph nodes, and thymus,
which also have stem cells for lymphocytes.
Red Blood Cells—erythrocytes (see Table
11–2 for normal values)
1. Biconcave discs; no nuclei when mature.
2. RBCs carry O2 bonded to the iron in hemoglobin.
3. RBCs are formed in the RBM from hemocytoblasts
(stem cells, the precursor cells).
4. Hypoxia stimulates the kidneys to produce the hormone
erythropoietin, which increases the rate of
RBC production in the RBM.
5. Immature RBCs: normoblasts (have nuclei) and
reticulocytes; large numbers in peripheral circulation
indicate a need for more RBCs to carry
oxygen.
6. Vitamin B12 is the extrinsic factor, needed for DNA
synthesis (mitosis) in stem cells in the RBM.
Intrinsic factor is produced by the parietal cells of
the stomach lining; it combines with B12 to prevent
its digestion and promote its absorption.
7. RBCs live for 120 days and are then phagocytized
by macrophages in the liver, spleen, and RBM. The
iron is returned to the RBM or stored in the liver.
The heme of the hemoglobin is converted to bilirubin,
which the liver excretes into bile to be eliminated
in feces. Colon bacteria change bilirubin to
urobilinogen. Any urobilinogen absorbed is converted
to urobilin and excreted by the kidneys in
urine (Fig. 11–4). Jaundice is the accumulation of
bilirubin in the blood, perhaps due to liver disease.
8. ABO blood types are hereditary. The type indicates
the antigen(s) on the RBCs (see Table 11–1 and
Fig. 11–5); antibodies in plasma are for those antigens
not present on the RBCs and are important
for transfusions.
9. The Rh type is also hereditary. Rh positive means
that the D antigen is present on the RBCs; Rh negative
means that the D antigen is not present on the
RBCs. Rh-negative people do not have natural
antibodies but will produce them if given Rhpositive
blood.
White Blood Cells—leukocytes (see Table
11–2 for normal values)
1. Larger than RBCs; have nuclei when mature; produced
in the red bone marrow, except some lymphocytes
produced in the thymus (Figs. 11–2 and
11–3).
2. Granular WBCs are the neutrophils, eosinophils,
and basophils.
3. Agranular WBCs are the lymphocytes and monocytes.
4. Neutrophils and monocytes phagocytize pathogens;
monocytes become macrophages, which also
phagocytize dead tissue.
5. Eosinophils detoxify foreign proteins during allergic
reactions and parasitic infections; they phagocytize
anything labeled with antibodies.
6. Basophils contain the anticoagulant heparin and
histamine, which contributes to inflammation.
7. Lymphocytes: T cells, B cells, and natural killer
cells. T cells recognize foreign antigens and destroy
them. B cells become plasma cells, which produce
antibodies to foreign antigens. NK cells
destroy foreign cell membranes.
8. WBCs carry out their functions in tissue fluid and
lymphatic tissue, as well as in the blood.
Platelets—thrombocytes (see Table 11–2 for
normal values)
1. Platelets are formed in the RBM and are fragments
of megakaryocytes; the hormone thrombopoietin
from the liver increases platelet production.
2. Platelets are involved in all mechanisms of hemostasis
(prevention of blood loss) (Fig. 11–6).
3. Vascular spasm—large vessels constrict when
damaged, the myogenic response. Platelets release
serotonin, which also causes vasoconstriction. The
break in the vessel is made smaller and may be
closed with a blood clot.
Blood 269
4. Platelet plugs—rupture of a capillary creates a
rough surface to which platelets stick and form a
barrier over the break.
5. Chemical clotting involves platelet factors, chemicals
from damaged tissue, prothrombin, fibrinogen
and other clotting factors synthesized by the liver,
and calcium ions. See Table 11–3 and Fig. 11–7 for
the three stages of chemical clotting. The clot is
formed of fibrin threads that form a mesh over the
break in the vessel.
6. Clot retraction is the folding of the fibrin threads
to pull the cut edges of the vessel closer together to
facilitate repair. Fibrinolysis is the dissolving of the
clot once it has served its purpose.
7. Abnormal clotting (thrombosis) is prevented by the
very smooth endothelium (simple squamous
epithelium) that lines blood vessels; heparin, which
inhibits the clotting process; and antithrombin
(synthesized by the liver), which inactivates excess
thrombin.
270 Blood
REVIEW QUESTIONS
1. Name four different kinds of substances transported
in blood plasma. (p. 252)
2. Name the precursor cell of all blood cells. Name
the primary hemopoietic tissue and state its locations.
(pp. 254)
3. State the normal values (CBC) for RBCs,
WBCs, platelets, hemoglobin, and hematocrit.
(p. 262)
4. State the function of RBCs; include the protein and
mineral needed. (p. 254)
5. Explain why iron, protein, folic acid, vitamin B12,
and the intrinsic factor are needed for RBC production.
(pp. 256)
6. Explain how bilirubin is formed and excreted.
(pp. 258–259)
7. Explain what will happen if a person with type O
positive blood receives a transfusion of type A negative
blood. (p. 261)
8. Name the WBC with each of the following functions:
(p. 262)
a. Become macrophages and phagocytize dead
tissue
b. Produce antibodies
c. Detoxify foreign proteins
d. Phagocytize pathogens
e. Contain the anticoagulant heparin
f. Recognize antigens as foreign
g. Secrete histamine during inflammation
9. Explain how and why platelet plugs form in ruptured
capillaries. (p. 264)
10. Explain how vascular spasm prevents excessive
blood loss when a large vessel is severed.
(p. 264)
11. With respect to chemical blood clotting:
(pp. 265–266)
a. Name the mineral necessary
b. Name the organ that produces many of the
clotting factors
c. Name the vitamin necessary for prothrombin
synthesis
d. State what the clot itself is made of
12. Explain what is meant by clot retraction and fibrinolysis.
(p. 266)
13. State two ways abnormal clotting is prevented in
the vascular system. (p. 268)
14. Explain what is meant by blood viscosity, the factors
that contribute, and why viscosity is important.
(p. 252)
15. State the normal pH range of blood. What gas has
an effect on blood pH? (p. 252)
16. Define anemia, leukocytosis, and thrombocytopenia.
(pp. 257, 263)
1. Explain why type AB blood may be called the
“universal recipient” for blood transfusions.
Explain why this would not be true if the transfusion
required 6 units (about 3 liters) of blood.
2. The liver has many functions that are directly
related to the composition and functions of blood.
Name as many as you can.
3. Constructing a brick wall requires bricks and bricklayers.
List all the nutrients that are needed for
RBC production, and indicate which are bricks and
which are bricklayers.
4. Anthony moved from New Jersey to a mountain
cabin in Colorado, 8000 feet above sea level. When
he first arrived, his hematocrit was 44%. After 6
months in his new home, what would you expect
his hematocrit to be? Explain your answer, and
what brought about the change.
5. The lab results for a particular patient show these
CBC values:
RBCs—4.2 million/ L
Hct—40%
Hb—13 g/100 mL
WBCs—8,500/ L
Platelets—30,000/ L
Is this patient healthy, or would you expect any
symptoms of a disorder? Explain your answer.
6. Using the model in Question 5, make a list of possible
CBC values for a patient with iron-deficiency
anemia. Then make a list of possible CBC values
for a person with aplastic anemia.
7. An artificial blood may someday be available; many
are being tested. What specific function of blood
will it definitely have? Are there any advantages to
an artificial blood compared with blood from a
human donor?
8. Disseminated intravascular coagulation (DIC) is a
serious condition that may follow certain kinds of
infections or traumas. First, explain what the name
means. This is best done one word at a time. In
DIC, clotting becomes a vicious cycle, and the
blood is depleted of clotting factors. What do
you think will be the consequence for the affected
person?
Blood 271
FOR FURTHER THOUGHT
272
CHAPTER 12
Chapter Outline
Location and Pericardial Membranes
Chambers—Vessels and Valves
Right Atrium
Left Atrium
Right Ventricle
Left Ventricle
Coronary Vessels
Cardiac Cycle and Heart Sounds
Cardiac Conduction Pathway
Heart Rate
Cardiac Output
Regulation of Heart Rate
Aging and the Heart
BOX 12–1 CORONARY ARTERY DISEASE
BOX 12–2 HEART MURMUR
BOX 12–3 ELECTROCARDIOGRAM
BOX 12–4 ARRHYTHMIAS
Student Objectives
• Describe the location of the heart, the pericardial
membranes, and the endocardium.
• Name the chambers of the heart and the vessels
that enter or leave each.
• Name the valves of the heart, and explain their
functions.
• Describe coronary circulation, and explain its purpose.
• Describe the cardiac cycle.
• Explain how heart sounds are created.
• Name the parts of the cardiac conduction pathway,
and explain why it is the sinoatrial node that initiates
each beat.
• Explain stroke volume, cardiac output, and
Starling’s law of the heart.
• Explain how the nervous system regulates heart
rate and force of contraction.
The Heart
273
New Terminology
Aorta (ay-OR-tah)
Atrium (AY-tree-um)
Cardiac cycle (KAR-dee-yak SIGH-kuhl)
Cardiac output (KAR-dee-yak OUT-put)
Coronary arteries (KOR-uh-na-ree AR-tuh-rees)
Diastole (dye-AS-tuh-lee)
Endocardium (EN-doh-KAR-dee-um)
Epicardium (EP-ee-KAR-dee-um)
Mediastinum (ME-dee-ah-STYE-num)
Mitral valve (MY-truhl VALV)
Myocardium (MY-oh-KAR-dee-um)
Sinoatrial (SA) node (SIGH-noh-AY-tree-al NOHD)
Stroke volume (STROHK VAHL-yoom)
Systole (SIS-tuh-lee)
Tricuspid valve (try-KUSS-pid VALV)
Venous return (VEE-nus ree-TURN)
Ventricle (VEN-tri-kuhl)
Related Clinical Terminology
Arrhythmia (uh-RITH-me-yah)
Ectopic focus (ek-TOP-ik FOH-kus)
Electrocardiogram (ECG) (ee-LEK-troh-KARdee-
oh-GRAM)
Fibrillation (fi-bri-LAY-shun)
Heart murmur (HART MUR-mur)
Ischemic (iss-KEY-mik)
Myocardial infarction (MY-oh-KAR-dee-yuhl
in-FARK-shun)
Pulse (PULS)
Stenosis (ste-NOH-sis)
Terms that appear in bold type in the chapter text are defined in the glossary, which begins on page 547.
In the embryo, the heart begins to beat at 4 weeks of
age, even before its nerve supply has been established.
If a person lives to be 80 years old, his or her heart
continues to beat an average of 100,000 times a day,
every day for each of those 80 years. Imagine trying to
squeeze a tennis ball 70 times a minute. After a few
minutes, your arm muscles would begin to tire. Then
imagine increasing your squeezing rate to 120 times a
minute. Most of us could not keep that up very long,
but that is what the heart does during exercise. A
healthy heart can increase its rate and force of contraction
to meet the body’s need for more oxygen,
then return to its resting rate and keep on beating as if
nothing very extraordinary had happened. In fact, it
isn’t extraordinary at all; this is the job the heart is
meant to do.
The primary function of the heart is to pump blood
through the arteries, capillaries, and veins. As you
learned in the previous chapter, blood transports oxygen
and nutrients and has other important functions
as well. The heart is the pump that keeps blood circulating
properly.
LOCATION AND
PERICARDIAL MEMBRANES
The heart is located in the thoracic cavity between the
lungs. This area is called the mediastinum. The base
of the cone-shaped heart is uppermost, behind the
sternum, and the great vessels enter or leave here. The
apex (tip) of the heart points downward and is just
above the diaphragm to the left of the midline. This is
why we may think of the heart as being on the left
side, because the strongest beat can be heard or felt
here.
The heart is enclosed in the pericardial membranes,
of which there are three layers (Fig. 12–1).
The outermost is the fibrous pericardium, a loosefitting
sac of strong fibrous connective tissue that
extends inferiorly over the diaphragm and superiorly
over the bases of the large vessels that enter and leave
the heart. The serous pericardium is a folded membrane;
the fold gives it two layers, parietal and visceral.
Lining the fibrous pericardium is the parietal pericardium.
On the surface of the heart muscle is the
visceral pericardium, often called the epicardium.
Between the parietal and visceral pericardial membranes
is serous fluid, which prevents friction as the
heart beats.
CHAMBERS—VESSELS AND VALVES
The walls of the four chambers of the heart are made
of cardiac muscle called the myocardium. The chambers
are lined with endocardium, simple squamous
epithelium that also covers the valves of the heart and
continues into the vessels as their lining (endothelium).
The important physical characteristic of the
endocardium is not its thinness, but rather its smoothness.
This very smooth tissue prevents abnormal
blood clotting, because clotting would be initiated by
contact of blood with a rough surface.
274 The Heart
Endocardium
Parietal
Myocardium pericardium
(heart muscle)
Epicardium
(visceral pericardium)
Fibrous pericardium
(pericardial sac)
Pericardial cavity
Figure 12–1. Layers of the wall of the heart and the
pericardial membranes. The endocardium is the lining of
the chambers of the heart. The fibrous pericardium is the
outermost layer.
QUESTION: What is found between the parietal and visceral
pericardial layers, and what is its function?
The upper chambers of the heart are the right and
left atria (singular: atrium), which have relatively thin
walls and are separated by a common wall of myocardium
called the interatrial septum. The lower chambers
are the right and left ventricles, which have
thicker walls and are separated by the interventricular
septum (Fig. 12–2). As you will see, the atria
receive blood, either from the body or the lungs, and
the ventricles pump blood to either the lungs or the
body.
RIGHT ATRIUM
The two large caval veins return blood from the body
to the right atrium (see Fig. 12–2). The superior vena
cava carries blood from the upper body, and the inferior
vena cava carries blood from the lower body.
From the right atrium, blood will flow through the
right atrioventricular (AV) valve, or tricuspid valve,
into the right ventricle.
The tricuspid valve is made of three flaps (or cusps)
of endocardium reinforced with connective tissue. The
general purpose of all valves in the circulatory system
is to prevent backflow of blood. The specific purpose
of the tricuspid valve is to prevent backflow of blood
from the right ventricle to the right atrium when the
right ventricle contracts. As the ventricle contracts,
blood is forced behind the three valve flaps, forcing
them upward and together to close the valve.
LEFT ATRIUM
The left atrium receives blood from the lungs, by way
of four pulmonary veins. This blood will then flow
into the left ventricle through the left atrioventricular
(AV) valve, also called the mitral valve or bicuspid
(two flaps) valve. The mitral valve prevents backflow
of blood from the left ventricle to the left atrium when
the left ventricle contracts.
Another function of the atria is the production of a
hormone involved in blood pressure maintenance.
When the walls of the atria are stretched by increased
blood volume or blood pressure, the cells produce
atrial natriuretic peptide (ANP), also called atrial
natriuretic hormone (ANH). (The ventricles of the
heart produce a similar hormone called B-type natriuretic
peptide, or BNP, but we will use ANP as the
representative cardiac hormone.) ANP decreases the
reabsorption of sodium ions by the kidneys, so that
more sodium ions are excreted in urine, which in turn
increases the elimination of water. The loss of water
lowers blood volume and blood pressure. You may
have noticed that ANP is an antagonist to the hormone
aldosterone, which raises blood pressure.
RIGHT VENTRICLE
When the right ventricle contracts, the tricuspid valve
closes and the blood is pumped to the lungs through
the pulmonary artery (or trunk). At the junction of this
large artery and the right ventricle is the pulmonary
semilunar valve (or more simply, pulmonary valve).
Its three flaps are forced open when the right ventricle
contracts and pumps blood into the pulmonary
artery. When the right ventricle relaxes, blood tends
to come back, but this fills the valve flaps and closes
the pulmonary valve to prevent backflow of blood into
the right ventricle.
Projecting into the lower part of the right ventricle
are columns of myocardium called papillary muscles
(see Fig. 12–2). Strands of fibrous connective tissue,
the chordae tendineae, extend from the papillary
muscles to the flaps of the tricuspid valve. When the
right ventricle contracts, the papillary muscles also
contract and pull on the chordae tendineae to prevent
inversion of the tricuspid valve. If you have ever had
your umbrella blown inside out by a strong wind, you
can see what would happen if the flaps of the tricuspid
valve were not anchored by the chordae tendineae and
papillary muscles.
LEFT VENTRICLE
The walls of the left ventricle are thicker than those of
the right ventricle, which enables the left ventricle to
contract more forcefully. The left ventricle pumps
blood to the body through the aorta, the largest artery
of the body. At the junction of the aorta and the left
ventricle is the aortic semilunar valve (or aortic
valve) (see Fig. 12–2). This valve is opened by the
force of contraction of the left ventricle, which also
closes the mitral valve. The aortic valve closes when
the left ventricle relaxes, to prevent backflow of blood
from the aorta to the left ventricle. When the mitral
(left AV) valve closes, it prevents backflow of blood to
the left atrium; the flaps of the mitral valve are also
anchored by chordae tendineae and papillary muscles.
All of the valves are shown in Fig. 12–3, which also
depicts the fibrous skeleton of the heart. This is
fibrous connective tissue that anchors the outer edges
The Heart 275
276 The Heart
Brachiocephalic (trunk) artery
Superior vena cava
Right pulmonary artery
Right atrium
Right coronary artery
Inferior vena cava
A
Left subclavian artery
Left internal jugular vein
Left common carotid artery
Aortic arch Left pulmonary artery
(to lungs)
Left atrium
Left pulmonary veins
(from lungs)
Circumflex artery
Left coronary artery
Left coronary vein
Left anterior descending
artery
Left ventricle
Right ventricle Aorta
Brachiocephalic artery
Superior vena cava
Left common carotid artery
Left subclavian artery
Aortic arch
Right pulmonary artery
Right pulmonary veins
Right pulmonary veins
Right atrium
Inferior vena cava
Tricuspid
valve
Pulmonary
semilunar valve
Left pulmonary artery
Left atrium
Left pulmonary veins
Mitral valve
Left ventricle
Aortic semilunar valve
Interventricular septum
Chordae Apex
tendineae Right ventricle
Papillary
muscles
B
Figure 12–2. (A) Anterior view of the heart and major blood vessels. (B) Frontal section
of the heart in anterior view, showing internal structures.
QUESTION: In part B, in the right atrium, what do the blue arrows represent?
of the valve flaps and keeps the valve openings from
stretching. It also separates the myocardium of the
atria and ventricles and prevents the contraction of
the atria from reaching the ventricles except by way of
the normal conduction pathway.
As you can see from this description of the chambers
and their vessels, the heart is really a double, or
two-sided, pump. The right side of the heart receives
deoxygenated blood from the body and pumps it to
the lungs to pick up oxygen and release carbon dioxide.
The left side of the heart receives oxygenated
blood from the lungs and pumps it to the body. Both
pumps work simultaneously; that is, both atria contract
together, followed by the contraction of both
ventricles. Aspects of the anatomy of the heart are
summarized in Table 12–1.
CORONARY VESSELS
The right and left coronary arteries are the first
branches of the ascending aorta, just beyond the aortic
semilunar valve (Fig. 12–4). The two arteries branch
into smaller arteries and arterioles, then to capillaries.
The coronary capillaries merge to form coronary
The Heart 277
Pulmonary semilunar
valve
Aortic semilunar
valve Tricuspid
valve
Fibrous
skeleton
Bicuspid (mitral) valve
Posterior
Coronary artery
Figure 12–3. Heart valves in superior view. The atria
have been removed. The fibrous skeleton of the heart is
also shown.
QUESTION: When do the mitral and tricuspid valves
close, and why is this important?
Table 12–1 ANATOMY OF THE HEART
Structure Description
Epicardium
Myocardium
Endocardium
Right atrium (RA)
Tricuspid valve
Right ventricle (RV)
Pulmonary semilunar valve
Left atrium (LA)
Mitral valve
Left ventricle (LV)
Aortic semilunar valve
Papillary muscles and
chordae tendineae
Fibrous skeleton of the heart
Serous membrane on the surface of the myocardium
Heart muscle; forms the walls of the four chambers
Endothelium that lines the chambers and covers the valves; smooth to prevent abnormal
clotting
Receives deoxygenated blood from the body by way of the superior and inferior caval
veins
Right AV valve; prevents backflow of blood from the RV to the RA when the RV
contracts
Pumps blood to the lungs by way of the pulmonary artery
Prevents backflow of blood from the pulmonary artery to the RV when the RV relaxes
Receives oxygenated blood from the lungs by way of the four pulmonary veins
Left AV valve; prevents backflow of blood from the LV to the LA when the LV contracts
Pumps blood to the body by way of the aorta
Prevents backflow of blood from the aorta to the LV when the LV relaxes
In both the RV and LV; prevent inversion of the AV valves when the ventricles contract
Fibrous connective tissue that anchors the four heart valves, prevents enlargement of
the valve openings, and electrically insulates the ventricles from the atria
veins, which empty blood into a large coronary sinus
that returns blood to the right atrium.
The purpose of the coronary vessels is to supply
blood to the myocardium itself, because oxygen is
essential for normal myocardial contraction. If a coronary
artery becomes obstructed, by a blood clot for
example, part of the myocardium becomes ischemic,
that is, deprived of its blood supply. Prolonged
ischemia will create an infarct, an area of necrotic
(dead) tissue. This is a myocardial infarction, commonly
called a heart attack (see also Box 12–1: Coronary
Artery Disease).
CARDIAC CYCLE
AND HEART SOUNDS
The cardiac cycle is the sequence of events in one
heartbeat. In its simplest form, the cardiac cycle is the
simultaneous contraction of the two atria, followed a
fraction of a second later by the simultaneous contraction
of the two ventricles. Systole is another term for
contraction. The term for relaxation is diastole. You
are probably familiar with these terms as they apply to
blood pressure readings. If we apply them to the cardiac
cycle, we can say that atrial systole is followed by
ventricular systole. There is, however, a significant
difference between the movement of blood from the
atria to the ventricles and the movement of blood
from the ventricles to the arteries. The events of the
cardiac cycle are shown in Fig. 12–5. In this traditional
representation, the cardiac cycle is depicted in a circle,
because one heartbeat follows another, and the beginning
of atrial systole is at the top (12 o’clock). The size
of the segment or arc of the circle indicates how long
it takes. Find the segment for atrial systole and the one
for ventricular systole, and notice how much larger
(meaning “longer”) ventricular systole is. Do you
think this might mean that ventricular contraction is
more important than atrial contraction? It does, as you
will see. Refer to Fig. 12–5 as you read the following.
We will begin at the bottom (6 o’clock) where the atria
are in the midst of diastole and the ventricles have just
completed their systole. The entire heart is relaxed
and the atria are filling with blood.
Blood is constantly flowing from the veins into
both atria. As more blood accumulates, its pressure
forces open the right and left AV valves. Two-thirds
of the atrial blood flows passively into the ventricles
(which brings us to 12 o’clock); the atria then
contract to pump the remaining blood into the ventricles.
Following their contraction, the atria relax and the
ventricles begin to contract. Ventricular contraction
forces blood against the flaps of the right and left AV
valves and closes them; the force of blood also opens
the aortic and pulmonary semilunar valves. As the
ventricles continue to contract, they pump blood into
the arteries. Notice that blood that enters the arteries
must all be pumped. The ventricles then relax, and at
the same time blood continues to flow into the atria,
and the cycle begins again.
278 The Heart
Aorta
Left coronary artery
Anterior
interventricular branch
Great cardiac
vein
Coronary sinus
Posterior
artery and
vein
Small
Right coronary artery cardiac vein
A and vein B
Figure 12–4. (A) Coronary vessels
in anterior view. The pulmonary
artery has been cut to show the left
coronary artery emerging from the
ascending aorta. (B) Coronary vessels
in posterior view. The coronary sinus
empties blood into the right atrium.
QUESTION: What is the function of
the coronary vessels?
The Heart 279
Ventricular diastole 0.5 sec
Atrial systole
0.1 sec
Most atrial blood
flows passively
into ventricles
Remainder
of atrial blood
is pumped into
ventricles
AV valves open
AV valves close
Semilunar valves open
Semilunar valves close
Ventricular systole 0.3 sec
Atrial diastole 0.7 sec
Ventricular blood
is pumped into
arteries
Figure 12–5. The cardiac cycle
depicted in one heartbeat (pulse: 75). The
outer circle represents the ventricles, the
middle circle the atria, and the inner circle
the movement of blood and its effect on
the heart valves. See text for description.
QUESTION: What makes the AV valves
close and the semilunar valves open?
The important distinction here is that most blood
flows passively from atria to ventricles, but all blood
to the arteries is actively pumped by the ventricles.
For this reason, the proper functioning of the ventricles
is much more crucial to survival than is atrial
functioning.
You may be asking “All this in one heartbeat?” The
answer is yes. The cardiac cycle is this precise
sequence of events that keeps blood moving from the
veins, through the heart, and into the arteries.
The cardiac cycle also creates the heart sounds:
Each heartbeat produces two sounds, often called lubdup,
that can be heard with a stethoscope. The first
sound, the loudest and longest, is caused by ventricular
systole closing the AV valves. The second sound is
caused by the closure of the aortic and pulmonary
semilunar valves. If any of the valves do not close
properly, an extra sound called a heart murmur may
be heard (see Box 12–2: Heart Murmur).
CARDIAC CONDUCTION PATHWAY
The cardiac cycle is a sequence of mechanical events
that is regulated by the electrical activity of the
myocardium. Cardiac muscle cells have the ability
to contract spontaneously; that is, nerve impulses are
not required to cause contraction. The heart generates
its own beat, and the electrical impulses follow a
very specific route throughout the myocardium. You
may find it helpful to refer to Fig. 12–6 as you read the
following.
The natural pacemaker of the heart is the sinoatrial
(SA) node, a specialized group of cardiac muscle cells
located in the wall of the right atrium just below the
opening of the superior vena cava. The SA node is
considered specialized because it has the most rapid
rate of contraction, that is, it depolarizes more rapidly
than any other part of the myocardium (60 to 80 times
per minute). As you may recall, depolarization is the
rapid entry of Na ions and the reversal of charges on
either side of the cell membrane. The cells of the SA
node are more permeable to Na ions than are other
cardiac muscle cells. Therefore, they depolarize more
rapidly, then contract and initiate each heartbeat.
From the SA node, impulses for contraction travel
to the atrioventricular (AV) node, located in the
lower interatrial septum. The transmission of impulses
from the SA node to the AV node and to the rest of the
atrial myocardium brings about atrial systole.
280 The Heart
BOX 12–1 CORONARY ARTERY DISEASE
Other predisposing factors for atherosclerosis
include cigarette smoking, diabetes mellitus, and
high blood pressure. Any one of these may cause
damage to the lining of coronary arteries, which is
the first step in the abnormal deposition of cholesterol.
A diet high in cholesterol and saturated fats
and high blood levels of these lipids will increase
the rate of cholesterol deposition.
A possible chemical marker of risk is a high blood
level of homocysteine. Homocysteine is a metabolic
product of the essential amino acid methionine,
and may be converted back to methionine or further
changed and excreted by the kidneys. A high
blood level of homocysteine may indicate inflammation
of the walls of arteries. Yet another chemical
marker of inflammation is C-reactive protein (CRP).
There is still much to learn about the role of inflammation
in atherosclerosis, but simple blood tests for
chemical markers may someday provide a diagnosis
before heart damage occurs.
When coronary artery disease becomes lifethreatening,
coronary artery bypass surgery may be
performed. In this procedure, a synthetic vessel or a
vein (such as the saphenous vein of the leg) is
grafted around the obstructed coronary vessel to
restore blood flow to the myocardium. This is not a
cure, for atherosclerosis may occur in a grafted vein
or at other sites in the coronary arteries.
Coronary artery disease results in decreased blood
flow to the myocardium. If blood flow is diminished
but not completely obstructed, the person may
experience difficulty breathing and angina, which is
chest pain caused by lack of oxygen to part of the
heart muscle. If blood flow is completely blocked,
however, the result is a myocardial infarction
(necrosis of cardiac muscle).
The most common cause of coronary artery disease
is atherosclerosis. Plaques of cholesterol form
in the walls of a coronary artery; this narrows the
lumen (cavity) and creates a rough surface where a
clot (thrombus) may form (see Box Fig. 12–A). A
predisposing factor for such clot formation, one that
cannot be changed, is a family history of coronary
artery disease. There is no “gene for heart attacks,”
but we do have genes for the enzymes involved in
cholesterol metabolism. Many of these are liver
enzymes that regulate the transport of cholesterol in
the blood in the form of lipoproteins and regulate
the liver’s excretion of excess cholesterol in bile.
Some people, therefore, have a greater tendency
than others to have higher blood levels of cholesterol
and certain lipoproteins. In women before
menopause, estrogen is believed to exert a protective
effect by lowering blood lipid levels. This is why
heart attacks in the 30- to 50-year-old age range are
less frequent in women than in men.
Normal artery Atherosclerotic artery
A B
Box Figure 12–A (A) Cross-section of normal coronary artery. (B) Coronary artery with
atherosclerosis narrowing the lumen.
Recall that the fibrous skeleton of the heart separates
the atrial myocardium from the ventricular
myocardium; the fibrous connective tissue acts as electrical
insulation between the two sets of chambers.
The only pathway for impulses from the atria to the
ventricles, therefore, is the atrioventricular bundle
(AV bundle), also called the bundle of His. The AV
bundle is within the upper interventricular septum; it
receives impulses from the AV node and transmits
them to the right and left bundle branches. From the
The Heart 281
SA node
Left atrium
Right
atrium
AV node
Right
ventricle
AV bundle
(Bundle of His)
Purkinje
fibers
Left ventricle
Left bundle branch
Right bundle branch
R
P wave
Q S
T wave
P-R Interval QRS
Complex
ST Segment
S-T Interval
Figure 12–6. Conduction pathway of the heart. Anterior view of the interior of the
heart. The electrocardiogram tracing is of one normal heartbeat. See text and Box 12–3 for
description.
QUESTION: What structure is the pacemaker of the heart, and what is its usual rate of
depolarization?
BOX 12–2 HEART MURMUR
close and prevent backflow during ventricular systole.
Some valve defects involve a narrowing (stenosis)
and are congenital; that is, the child is born with
an abnormally narrow valve. In aortic stenosis, for
example, blood cannot easily pass from the left ventricle
to the aorta. The ventricle must then work
harder to pump blood through the narrow valve to
the arteries, and the turbulence created is also heard
as a systolic murmur.
Children sometimes have heart murmurs that
are called “functional” because no structural cause
can be found. These murmurs usually disappear
with no adverse effects on the child.
A heart murmur is an abnormal or extra heart sound
caused by a malfunctioning heart valve. The function
of heart valves is to prevent backflow of blood,
and when a valve does not close properly, blood will
regurgitate (go backward), creating turbulence that
may be heard with a stethoscope.
Rheumatic heart disease is a now uncommon
complication of a streptococcal infection. In rheumatic
fever, the heart valves are damaged by an
abnormal response by the immune system. Erosion
of the valves makes them “leaky” and inefficient,
and a murmur of backflowing blood will be heard.
Mitral valve regurgitation, for example, will be heard
as a systolic murmur, because this valve is meant to
bundle branches, impulses travel along Purkinje
fibers to the rest of the ventricular myocardium and
bring about ventricular systole. The electrical activity
of the atria and ventricles is depicted by an electrocardiogram
(ECG); this is discussed in Box 12–3:
Electrocardiogram.
If the SA node does not function properly, the AV
node will initiate the heartbeat, but at a slower rate (50
to 60 beats per minute). The AV bundle is also capable
of generating the beat of the ventricles, but at a
much slower rate (15 to 40 beats per minute). This
may occur in certain kinds of heart disease in which
transmission of impulses from the atria to the ventricles
is blocked.
Arrhythmias are irregular heartbeats; their effects
range from harmless to life-threatening. Nearly
everyone experiences heart palpitations (becoming
aware of an irregular beat) from time to time. These
are usually not serious and may be the result of
too much caffeine, nicotine, or alcohol. Much more
serious is ventricular fibrillation, a very rapid and
uncoordinated ventricular beat that is totally inef-
282 The Heart
BOX 12–3 ELECTROCARDIOGRAM
throughout the ventricular myocardium. The T
wave represents repolarization of the ventricles
(atrial repolarization does not appear as a separate
wave because it is masked by the QRS complex).
Detailed interpretation of abnormal ECGs is
beyond the scope of this book, but in general, the
length of each wave and the time intervals between
waves are noted. An ECG may be helpful in the
diagnosis of coronary atherosclerosis, which deprives
the myocardium of oxygen, or of rheumatic
fever or other valve disorders that result in enlargement
of a chamber of the heart and prolong a specific
wave of an ECG. For example, the enlargement
of the left ventricle that is often a consequence of
hypertension may be indicated by an abnormal
QRS complex.
A heartbeat is a series of electrical events, and the
electrical changes generated by the myocardium
can be recorded by placing electrodes on the body
surface. Such a recording is called an electrocardiogram
(ECG) (see Fig. 12–6).
A typical ECG consists of three distinguishable
waves or deflections: the P wave, the QRS complex,
and the T wave. Each represents a specific electrical
event; all are shown in Fig. 12–6 in a normal ECG
tracing.
The P wave represents depolarization of the
atria, that is, the transmission of electrical impulses
from the SA node throughout the atrial myocardium.
The QRS complex represents depolarization of
the ventricles as the electrical impulses spread
BOX 12–4 ARRHYTHMIAS
rillating ventricles are not pumping, and cardiac
output decreases sharply.
Ventricular fibrillation may follow a non-fatal
heart attack (myocardial infarction). Damaged cardiac
muscle cells may not be able to maintain a normal
state of polarization, and they depolarize
spontaneously and rapidly. From this ectopic focus,
impulses spread to other parts of the ventricular
myocardium in a rapid and haphazard pattern, and
the ventricles quiver rather than contract as a unit.
It is often possible to correct ventricular fibrillation
with the use of an electrical defibrillator. This
instrument delivers an electric shock to the heart,
which causes the entire myocardium to depolarize
and contract, then relax. If the first part of the heart
to recover is the SA node (which usually has the
most rapid rate of contraction), a normal heartbeat
may be restored.
Arrhythmias (also called dysrhythmias) are irregular
heartbeats caused by damage to part of the
conduction pathway, or by an ectopic focus,
which is a beat generated in part of the
myocardium other than the SA node.
Flutter is a very rapid but fairly regular heartbeat.
In atrial flutter, the atria may contract up to
300 times per minute. Because atrial pumping is
not crucial, however, blood flow to the ventricles
may be maintained for a time, and flutter may not
be immediately life-threatening. Ventricular flutter
is usually only a brief transition between ventricular
tachycardia and fibrillation.
Fibrillation is very rapid and uncoordinated
contractions. Ventricular fibrillation is a medical
emergency that must be quickly corrected to prevent
death. Normal contraction of the ventricles is
necessary to pump blood into the arteries, but fib-
fective for pumping blood (see Box 12–4: Arrhythmias).
HEART RATE
A healthy adult has a resting heart rate (pulse) of 60 to
80 beats per minute, which is the rate of depolarization
of the SA node. (The SA node actually has a
slightly faster rate, closer to 100 beats per minute, but
is slowed by parasympathetic nerve impulses to what
we consider a normal resting rate.) A rate less than 60
(except for athletes) is called bradycardia; a prolonged
or consistent rate greater than 100 beats per minute is
called tachycardia.
A child’s normal heart rate may be as high as 100
beats per minute, that of an infant as high as 120, and
that of a near-term fetus as high as 140 beats per
minute. These higher rates are not related to age, but
rather to size: the smaller the individual, the higher the
metabolic rate and the faster the heart rate. Parallels
may be found among animals of different sizes; the
heart rate of a mouse is about 200 beats per minute
and that of an elephant about 30 beats per minute.
Let us return to the adult heart rate and consider
the person who is in excellent physical condition. As
you may know, well-conditioned athletes have low
resting pulse rates. Those of basketball players are
often around 50 beats per minute, and the pulse of a
marathon runner often ranges from 35 to 40 beats per
minute. To understand why this is so, remember that
the heart is a muscle. When our skeletal muscles are
exercised, they become stronger and more efficient.
The same is true for the heart; consistent exercise
makes it a more efficient pump, as you will see in the
next section.
CARDIAC OUTPUT
Cardiac output is the amount of blood pumped by a
ventricle in 1 minute. A certain level of cardiac output
is needed at all times to transport oxygen to tissues and
to remove waste products. During exercise, cardiac
output must increase to meet the body’s need for more
oxygen. We will return to exercise after first considering
resting cardiac output.
To calculate cardiac output, we must know the
pulse rate and how much blood is pumped per beat.
Stroke volume is the term for the amount of blood
pumped by a ventricle per beat; an average resting
stroke volume is 60 to 80 mL per beat. A simple formula
then enables us to determine cardiac output:
Cardiac output stroke volume pulse (heart rate)
Let us put into this formula an average resting
stroke volume, 70 mL, and an average resting pulse,
70 beats per minute (bpm):
Cardiac output 70 mL 70 bpm
Cardiac output 4900 mL per minute
(approximately 5 liters)
Naturally, cardiac output varies with the size of the
person, but the average resting cardiac output is 5 to 6
liters per minute. Notice that this amount is just about
the same as a person’s average volume of blood. At
rest, the heart pumps all of the blood in the body
within about a minute. Changes are possible, depending
on circumstances and extent of physical activity.
If we now reconsider the athlete, you will be able to
see precisely why the athlete has a low resting pulse. In
our formula, we will use an average resting cardiac
output (5 liters) and an athlete’s pulse rate (50):
Cardiac output stroke volume pulse
5000 mL stroke volume 50 bpm
5000/50 stroke volume
100 mL stroke volume
Notice that the athlete’s resting stroke volume is
significantly higher than the average. The athlete’s
more efficient heart pumps more blood with each beat
and so can maintain a normal resting cardiac output
with fewer beats.
Now let us see how the heart responds to exercise.
Heart rate (pulse) increases during exercise, and so
does stroke volume. The increase in stroke volume is
the result of Starling’s law of the heart, which states
that the more the cardiac muscle fibers are stretched,
the more forcefully they contract. During exercise,
more blood returns to the heart; this is called venous
return. Increased venous return stretches the myocardium
of the ventricles, which contract more forcefully
and pump more blood, thereby increasing stroke volume.
Therefore, during exercise, our formula might
be the following:
Cardiac output stroke volume pulse
Cardiac output 100 mL 100 bpm
Cardiac output 10,000 mL (10 liters)
The Heart 283
This exercise cardiac output is twice the resting
cardiac output we first calculated, which should not be
considered unusual. The cardiac output of a healthy
young person may increase up to four times the resting
level during strenuous exercise. This difference is
the cardiac reserve, the extra volume the heart can
pump when necessary. If resting cardiac output is 5
liters and exercise cardiac output is 20 liters, the cardiac
reserve is 15 liters. The marathon runner’s cardiac
output may increase six times or more compared to
the resting level, and cardiac reserve is even greater
than for the average young person; this is the result of
the marathoner’s extremely efficient heart. Because of
Starling’s law, it is almost impossible to overwork a
healthy heart. No matter how much the volume of
venous return increases, the ventricles simply pump
more forcefully and increase the stroke volume and
cardiac output.
Also related to cardiac output, and another measure
of the health of the heart, is the ejection fraction.
This is the percent of the blood in a ventricle that is
pumped during systole. A ventricle does not empty
completely when it contracts, but should pump out
60% to 70% of the blood within it. A lower percentage
would indicate that the ventricle is weakening.
These aspects of physiology are summarized in Table
12–2.
REGULATION OF HEART RATE
Although the heart generates and maintains its own
beat, the rate of contraction can be changed to adapt
to different situations. The nervous system can and
does bring about necessary changes in heart rate as
well as in force of contraction.
The medulla of the brain contains the two cardiac
centers, the accelerator center and the inhibitory
center. These centers send impulses to the heart
along autonomic nerves. Recall from Chapter 8 that
the autonomic nervous system has two divisions: sympathetic
and parasympathetic. Sympathetic impulses
from the accelerator center along sympathetic nerves
increase heart rate and force of contraction during
exercise and stressful situations. Parasympathetic
impulses from the inhibitory center along the vagus
nerves decrease the heart rate. At rest these impulses
slow down the depolarization of the SA node to what
we consider a normal resting rate, and they also slow
the heart after exercise is over.
Our next question might be: What information is
received by the medulla to initiate changes? Because
the heart pumps blood, it is essential to maintain normal
blood pressure. Blood contains oxygen, which all
tissues must receive continuously. Therefore, changes
in blood pressure and oxygen level of the blood are
stimuli for changes in heart rate.
You may also recall from Chapter 9 that pressoreceptors
and chemoreceptors are located in the
carotid arteries and aortic arch. Pressoreceptors in
the carotid sinuses and aortic sinus detect changes in
blood pressure. Chemoreceptors in the carotid
bodies and aortic body detect changes in the oxygen
content of the blood. The sensory nerves for the
carotid receptors are the glossopharyngeal (9th cranial)
nerves; the sensory nerves for the aortic arch
284 The Heart
Table 12–2 PHYSIOLOGY OF THE HEART
Aspect and
Normal Range Description
Heart rate (pulse):
60–80 bpm
Stroke volume:
60–80 mL/beat
Cardiac output:
5–6 L/min
Ejection fraction:
60%–70%
Cardiac reserve:
15 liters or more
Generated by the SA node, propagated through the conduction pathway; parasympathetic
impulses (vagus nerves) decrease the rate; sympathetic impulses increase the rate
The amount of blood pumped by a ventricle in one beat
The volume of blood pumped by a ventricle in 1 minute; stroke volume x pulse
The percentage of blood within a ventricle that is pumped out per beat
The difference between resting cardiac output and maximum cardiac output during exercise
receptors are the vagus (10th cranial) nerves. If we
now put all of these facts together in a specific example,
you will see that the regulation of heart rate is a
reflex. Figure 12–7 depicts all of the structures just
mentioned.
A person who stands up suddenly from a lying position
may feel light-headed or dizzy for a few moments,
because blood pressure to the brain has decreased
abruptly. The drop in blood pressure is detected by
pressoreceptors in the carotid sinuses—notice that
they are “on the way” to the brain, a very strategic
location. The drop in blood pressure causes fewer
impulses to be generated by the pressoreceptors.
These impulses travel along the glossopharyngeal
nerves to the medulla, and the decrease in the frequency
of impulses stimulates the accelerator center.
The accelerator center generates impulses that are carried
by sympathetic nerves to the SA node, AV node,
and ventricular myocardium. As heart rate and force
increase, blood pressure to the brain is raised to normal,
and the sensation of light-headedness passes.
When blood pressure to the brain is restored to normal,
the heart receives more parasympathetic impulses
from the inhibitory center along the vagus nerves to
the SA node and AV node. These parasympathetic
impulses slow the heart rate to a normal resting pace.
The heart will also be the effector in a reflex stimulated
by a decrease in the oxygen content of the
blood. The aortic receptors are strategically located so
as to detect such an important change as soon as blood
leaves the heart. The reflex arc in this situation would
be (1) aortic chemoreceptors, (2) vagus nerves (sensory),
(3) accelerator center in the medulla, (4) sympathetic
nerves, and (5) the heart muscle, which will
increase its rate and force of contraction to circulate
more oxygen to correct the hypoxia.
Recall also from Chapter 10 that the hormone
epinephrine is secreted by the adrenal medulla in
stressful situations. One of the many functions of epinephrine
is to increase heart rate and force of contraction.
This will help supply more blood to tissues in
need of more oxygen.
The Heart 285
Accelerator center
Inhibitory center
Medulla
Thoracic spinal cord
Sympathetic nerves
Right ventricle
Vagus (motor) nerves
Vagus (sensory)
nerve
Glossopharyngeal
nerves
Carotid sinus and
carotid body
Common
carotid
arteries
Aortic arch
Aortic sinus
and aortic body
SA node
Bundle of His
AV node
Figure 12–7. Nervous regulation of the heart. The brain and spinal cord are shown on
the left. The heart and major blood vessels are shown on the right.
QUESTION: Sympathetic impulses to the ventricles will have what effect?
The heart pumps blood, which creates blood
pressure, and circulates oxygen, nutrients,
and other substances. The heart is located in
the mediastinum, the area between the
lungs in the thoracic cavity.
Pericardial Membranes—three layers that
enclose the heart (see Fig. 12–1)
1. The outer, fibrous pericardium, made of fibrous
connective tissue, is a loose-fitting sac that surrounds
the heart and extends over the diaphragm
and the bases of the great vessels.
2. The parietal pericardium is a serous membrane
that lines the fibrous pericardium.
3. The visceral pericardium, or epicardium, is a serous
membrane on the surface of the myocardium.
4. Serous fluid between the parietal and visceral pericardial
membranes prevents friction as the heart
beats.
Chambers of the Heart (see Fig. 12–2 and
Table 12–1)
1. Cardiac muscle tissue, the myocardium, forms the
walls of the four chambers of the heart.
2. Endocardium lines the chambers and covers the
valves of the heart; is simple squamous epithelium
that is very smooth and prevents abnormal clotting.
3. The right and left atria are the upper chambers,
separated by the interatrial septum. The atria
receive blood from veins.
4. The right and left ventricles are the lower chambers,
separated by the interventricular septum. The
ventricles pump blood into arteries.
Right Atrium
1. Receives blood from the upper body by way of the
superior vena cava and receives blood from the
lower body by way of the inferior vena cava.
2. The tricuspid (right AV) valve prevents backflow of
blood from the right ventricle to the right atrium
when the right ventricle contracts.
Left Atrium
1. Receives blood from the lungs by way of four pulmonary
veins.
2. The mitral (left AV or bicuspid) valve prevents
backflow of blood from the left ventricle to the left
atrium when the left ventricle contracts.
3. The walls of the atria produce atrial natriuretic
peptide when stretched by increased blood volume
or BP. ANP increases the loss of Na ions and
water in urine, which decreases blood volume and
BP to normal.
286 The Heart
STUDY OUTLINE
AGING AND THE HEART
The heart muscle becomes less efficient with age, and
there is a decrease in both maximum cardiac output
and heart rate, although resting levels may be more
than adequate. The health of the myocardium
depends on its blood supply, and with age there is
greater likelihood that atherosclerosis will narrow the
coronary arteries. Atherosclerosis is the deposition of
cholesterol on and in the walls of the arteries, which
decreases blood flow and forms rough surfaces that
may cause intravascular clot formation.
High blood pressure (hypertension) causes the left
ventricle to work harder; it may enlarge and outgrow
its blood supply, thus becoming weaker. A weak ventricle
is not an efficient pump, and such weakness may
progress to congestive heart failure; such a progression
may be slow, or may be rapid. The heart valves
may become thickened by fibrosis, leading to heart
murmurs and less efficient pumping. Arrhythmias are
also more common with age, as the cells of the conduction
pathway become less efficient.
SUMMARY
As you can see, the nervous system regulates the functioning
of the heart based on what the heart is supposed
to do. The pumping of the heart maintains
normal blood pressure and proper oxygenation of tissues,
and the nervous system ensures that the heart
will be able to meet these demands in different situations.
Blood pressure and the blood vessels are the
subjects of the next chapter.
Right Ventricle—has relatively thin walls
1. Pumps blood to the lungs through the pulmonary
artery.
2. The pulmonary semilunar valve prevents backflow
of blood from the pulmonary artery to the right
ventricle when the right ventricle relaxes.
3. Papillary muscles and chordae tendineae prevent
inversion of the right AV valve when the right ventricle
contracts.
Left Ventricle—has thicker walls than does
the right ventricle
1. Pumps blood to the body through the aorta.
2. The aortic semilunar valve prevents backflow of
blood from the aorta to the left ventricle when the
left ventricle relaxes.
3. Papillary muscles and chordae tendineae prevent
inversion of the left AV valve when the left ventricle
contracts.
4. The heart is a double pump: The right side of the
heart receives deoxygenated blood from the body
and pumps it to the lungs; the left side of the heart
receives oxygenated blood from the lungs and
pumps it to the body. Both sides of the heart work
simultaneously.
Coronary Vessels (see Fig. 12–4)
1. Pathway: ascending aorta to right and left coronary
arteries, to smaller arteries, to capillaries, to coronary
veins, to the coronary sinus, to the right
atrium.
2. Coronary circulation supplies oxygenated blood to
the myocardium.
3. Obstruction of a coronary artery causes a myocardial
infarction: death of an area of myocardium due
to lack of oxygen.
Cardiac Cycle—the sequence of events in one
heartbeat (see Fig. 12–5)
1. The atria continually receive blood from the veins;
as pressure within the atria increases, the AV valves
are opened.
2. Two-thirds of the atrial blood flows passively
into the ventricles; atrial contraction pumps the
remaining blood into the ventricles; the atria then
relax.
3. The ventricles contract, which closes the AV valves
and opens the aortic and pulmonary semilunar
valves.
4. Ventricular contraction pumps all blood into the
arteries. The ventricles then relax. Meanwhile,
blood is filling the atria, and the cycle begins again.
5. Systole means contraction; diastole means relaxation.
In the cardiac cycle, atrial systole is followed
by ventricular systole. When the ventricles are in
systole, the atria are in diastole.
6. The mechanical events of the cardiac cycle keep
blood moving from the veins through the heart and
into the arteries.
Heart Sounds—two sounds per heartbeat:
lub-dup
1. The first sound is created by closure of the AV
valves during ventricular systole.
2. The second sound is created by closure of the aortic
and pulmonary semilunar valves.
3. Improper closing of a valve results in a heart murmur.
Cardiac Conduction Pathway—the pathway
of impulses during the cardiac cycle (see Fig.
12–6)
1. The SA node in the wall of the right atrium initiates
each heartbeat; the cells of the SA node are
more permeable to Na ions and depolarize more
rapidly than any other part of the myocardium.
2. The AV node is in the lower interatrial septum.
Depolarization of the SA node spreads to the AV
node and to the atrial myocardium and brings
about atrial systole.
3. The AV bundle (bundle of His) is in the upper
interventricular septum; the first part of the ventricles
to depolarize.
4. The right and left bundle branches in the interventricular
septum transmit impulses to the Purkinje
fibers in the ventricular myocardium, which complete
ventricular systole.
5. An electrocardiogram (ECG) depicts the electrical
activity of the heart (see Fig. 12–6).
6. If part of the conduction pathway does not function
properly, the next part will initiate contraction, but
at a slower rate.
7. Arrhythmias are irregular heartbeats; their effects
range from harmless to life-threatening.
Heart Rate
1. Healthy adult: 60 to 80 beats per minute (heart rate
equals pulse); children and infants have faster
The Heart 287
pulses because of their smaller size and higher
metabolic rate.
2. A person in excellent physical condition has a slow
resting pulse because the heart is a more efficient
pump and pumps more blood per beat.
Cardiac Output (see Table 12–2)
1. Cardiac output is the amount of blood pumped by
a ventricle in 1 minute.
2. Stroke volume is the amount of blood pumped by a
ventricle in one beat; average is 60 to 80 mL.
3. Cardiac output equals stroke volume pulse; average
resting cardiac output is 5 to 6 liters.
4. Starling’s law of the heart—the more cardiac muscle
fibers are stretched, the more forcefully they
contract.
5. During exercise, stroke volume increases as venous
return increases and stretches the myocardium of
the ventricles (Starling’s law).
6. During exercise, the increase in stroke volume and
the increase in pulse result in an increase in cardiac
output: two to four times the resting level.
7. Cardiac reserve is the difference between resting
cardiac output and the maximum cardiac output;
may be 15 liters or more.
8. The ejection fraction is the percent of its total
blood that a ventricle pumps per beat; average is
60% to 70%.
Regulation of Heart Rate (see Fig. 12–7)
1. The heart generates its own beat, but the nervous
system brings about changes to adapt to different
situations.
2. The medulla contains the cardiac centers: the
accelerator center and the inhibitory center.
3. Sympathetic impulses to the heart increase rate and
force of contraction; parasympathetic impulses
(vagus nerves) to the heart decrease heart rate.
4. Pressoreceptors in the carotid and aortic sinuses
detect changes in blood pressure.
5. Chemoreceptors in the carotid and aortic bodies
detect changes in the oxygen content of the blood.
6. The glossopharyngeal nerves are sensory for the
carotid receptors. The vagus nerves are sensory for
the aortic receptors.
7. If blood pressure to the brain decreases, pressoreceptors
in the carotid sinuses detect this decrease
and send fewer sensory impulses along the glossopharyngeal
nerves to the medulla. The accelerator
center dominates and sends motor impulses
along sympathetic nerves to increase heart rate and
force of contraction to restore blood pressure to
normal.
8. A similar reflex is activated by hypoxia.
9. Epinephrine from the adrenal medulla increases
heart rate and force of contraction during stressful
situations.
288 The Heart
REVIEW QUESTIONS
1. Describe the location of the heart with respect to
the lungs and to the diaphragm. (p. 274)
2. Name the three pericardial membranes. Where
is serous fluid found and what is its function?
(p. 274)
3. Describe the location and explain the function of
endocardium. (p. 274)
4. Name the veins that enter the right atrium; name
those that enter the left atrium. For each, where
does the blood come from? (p. 275)
5. Name the artery that leaves the right ventricle;
name the artery that leaves the left ventricle. For
each, where is the blood going? (p. 275)
6. Explain the purpose of the right and left AV valves
and the purpose of the aortic and pulmonary semilunar
valves. (p. 275)
7. Describe the coronary system of vessels and
explain the purpose of coronary circulation. (p.
278)
8. Define systole, diastole, and cardiac cycle.
(p. 278)
9. Explain how movement of blood from atria to
ventricles differs from movement of blood from
ventricles to arteries. (p. 279)
10. Explain why the heart is considered a double
pump. Trace the path of blood from the right
atrium back to the right atrium, naming the
chambers of the heart and their vessels through
which the blood passes. (pp. 275, 277)
11. Name the parts, in order, of the cardiac conduction
pathway. Explain why it is the SA node that
generates each heartbeat. State a normal range of
heart rate for a healthy adult. (pp. 279–283)
12. Calculate cardiac output if stroke volume is 75
mL and pulse is 75 bpm. Using the cardiac output
you just calculated as a resting normal, what is the
stroke volume of a marathoner whose resting
pulse is 40 bpm? (p. 283)
13. Name the two cardiac centers and state their location.
Sympathetic impulses to the heart have what
effect? Parasympathetic impulses to the heart
have what effect? Name the parasympathetic
nerves to the heart. (p. 284)
14. State the locations of arterial pressoreceptors and
chemoreceptors, what they detect, and their sensory
nerves. (p. 284)
15. Describe the reflex arc to increase heart rate and
force when blood pressure to the brain decreases.
(p. 285)
The Heart 289
FOR FURTHER THOUGHT
1. Endocarditis may be caused by bacteria or fungi
that erode, or wear away, the heart valves, or in
some cases make the valves bumpy (these bumps
are called vegetations—think cauliflower). Explain
the possible consequences of this.
2. Bob, a college freshman, is telling his new friends
that he has been running seriously for 6 years,
and can run a marathon in a little over 3 hours. His
friends aren’t sure they should believe him, but
don’t want to spend 3 hours waiting while Bob
runs 26 miles. Bob says that he can prove he is
telling the truth in 1 minute. Can he? Explain why
or why not.
3. A neighbor, Mrs. G., age 62, tells you that she
“doesn’t feel right” and is suddenly tired for no
apparent reason. She denies having chest pain,
though she admits to a “full” feeling she calls indigestion.
You suspect that she may be having a heart
attack. What question can you ask to help you be
more sure? Explain the physiological basis for your
question.
4. Several types of artificial hearts are being developed
and tested. What are the three essential
characteristics a truly useful artificial heart must
have? One is obvious, the others, perhaps not as
much so.
290
CHAPTER 13
C
Chapter Outline
Arteries
Veins
Anastomoses
Capillaries
Exchanges in Capillaries
Pathways of Circulation
Pulmonary Circulation
Systemic Circulation
Hepatic Portal Circulation
Fetal Circulation
Velocity of Blood Flow
Blood Pressure
Maintenance of Systemic Blood Pressure
Distribution of Blood Flow
Regulation of Blood Pressure
Intrinsic Mechanisms
Nervous Mechanisms
Aging and the Vascular System
BOX 13–1 DISORDERS OF ARTERIES
BOX 13–2 DISORDERS OF VEINS
BOX 13–3 PULSE SITES
BOX 13–4 HYPERTENSION
BOX 13–5 CIRCULATORY SHOCK
Student Objectives
• Describe the structure of arteries and veins, and
relate their structure to function.
• Explain the purpose of arterial and venous anastomoses.
• Describe the structure of capillaries, and explain
the exchange processes that take place in capillaries.
• Describe the pathway and purpose of pulmonary
circulation.
• Name the branches of the aorta and their distributions.
• Name the major systemic veins, and the parts of
the body they drain of blood.
• Describe the pathway and purpose of hepatic portal
circulation.
• Describe the modifications of fetal circulation, and
explain the purpose of each.
• Explain the importance of slow blood flow in capillaries.
• Define blood pressure, and state the normal
ranges for systemic and pulmonary blood pressure.
• Explain the factors that maintain systemic blood
pressure.
• Explain how the heart and kidneys are involved in
the regulation of blood pressure.
• Explain how the medulla and the autonomic nervous
system regulate the diameter of blood vessels.
The Vascular System
291
New Terminology
Anastomosis (a-NAS-ti-MOH-sis)
Arteriole (ar-TIR-ee-ohl)
Circle of Willis (SIR-kuhl of WILL-iss)
Ductus arteriosus (DUK-tus ar-TIR-ee-OH-sis)
Foramen ovale (for-RAY-men oh-VAHL-ee)
Hepatic portal (hep-PAT-ik POOR-tuhl)
Peripheral resistance (puh-RIFF-uh-ruhl ree-ZIStense)
Placenta (pluh-SEN-tah)
Precapillary sphincter (pre-KAP-i-lar-ee SFINK-ter)
Sinusoid (SIGH-nuh-soyd)
Umbilical arteries (uhm-BILL-i-kull AR-tuh-rees)
Umbilical vein (uhm-BILL-i-kull VAIN)
Venule (VEN-yool)
Related Clinical Terminology
Anaphylactic (AN-uh-fi-LAK-tik)
Aneurysm (AN-yur-izm)
Arteriosclerosis (ar-TIR-ee-oh-skle-ROH-sis)
Hypertension (HIGH-per-TEN-shun)
Hypovolemic (HIGH-poh-voh-LEEM-ik)
Phlebitis (fle-BY-tis)
Pulse deficit (PULS DEF-i-sit)
Septic shock (SEP-tik SHAHK)
Varicose veins (VAR-i-kohs VAINS).
Terms that appear in bold type in the chapter text are defined in the glossary, which begins on page 547.
The role of blood vessels in the circulation of blood
has been known since 1628, when William Harvey, an
English anatomist, demonstrated that blood in veins
always flowed toward the heart. Before that time, it
was believed that blood was static or stationary, some
of it within the vessels but the rest sort of in puddles
throughout the body. Harvey showed that blood
indeed does move, and only in the blood vessels
(though he did not know of the existence of capillaries).
In the centuries that followed, the active (rather
than merely passive) roles of the vascular system were
discovered, and all contribute to homeostasis.
The vascular system consists of the arteries, capillaries,
and veins through which the heart pumps blood
throughout the body. As you will see, the major “business”
of the vascular system, which is the exchange of
materials between the blood and tissues, takes place in
the capillaries. The arteries and veins, however, are
just as important, transporting blood between the capillaries
and the heart.
Another important topic of this chapter will be
blood pressure (BP), which is the force the blood
exerts against the walls of the vessels. Normal blood
pressure is essential for circulation and for some of the
material exchanges that take place in capillaries.
ARTERIES
Arteries carry blood from the heart to capillaries;
smaller arteries are called arterioles. If we look at an
artery in cross-section, we find three layers (or tunics)
of tissues, each with different functions (Fig. 13–1).
The innermost layer, the tunica intima, is the only
part of a vessel that is in contact with blood. It is made
of simple squamous epithelium called endothelium.
This lining is the same type of tissue that forms the
endocardium, the lining of the chambers of the heart.
As you might guess, its function is also the same: Its
extreme smoothness prevents abnormal blood clotting.
The endothelium of vessels, however, also produces
nitric oxide (NO), which is a vasodilator. The
tunica media, or middle layer, is made of smooth
muscle and elastic connective tissue. Both of these tissues
are involved in the maintenance of normal blood
pressure, especially diastolic blood pressure when the
heart is relaxed. The smooth muscle is the tissue
affected by the vasodilator NO; relaxation of this muscle
tissue brings about dilation of the vessel. Smooth
muscle also has a nerve supply; sympathetic nerve
impulses bring about vasoconstriction. Fibrous connective
tissue forms the outer layer, the tunica
externa. This tissue is very strong, which is important
to prevent the rupture or bursting of the larger arteries
that carry blood under high pressure (see Box 13–1:
Disorders of Arteries).
The outer and middle layers of large arteries are
quite thick. In the smallest arterioles, only individual
smooth muscle cells encircle the tunica intima. As
mentioned, the smooth muscle layer enables arteries
to constrict or dilate. Such changes in diameter are
regulated by the medulla and autonomic nervous system,
and will be discussed in a later section on blood
pressure.
VEINS
Veins carry blood from capillaries back to the heart;
the smaller veins are called venules. The same three
tissue layers are present in veins as in the walls of
arteries, but there are some differences when compared
to the arterial layers. The inner layer of veins is
smooth endothelium, but at intervals this lining is
folded to form valves (see Fig. 13–1). Valves prevent
backflow of blood and are most numerous in veins of
the legs, where blood must often return to the heart
against the force of gravity.
The middle layer of veins is a thin layer of smooth
muscle. It is thin because veins do not regulate blood
pressure and blood flow into capillaries as arteries do.
Veins can constrict extensively, however, and this
function becomes very important in certain situations
such as severe hemorrhage. The outer layer of veins is
also thin; not as much fibrous connective tissue is necessary
because blood pressure in veins is very low.
ANASTOMOSES
An anastomosis is a connection, or joining, of vessels,
that is, artery to artery or vein to vein. The general
purpose of these connections is to provide alternate
pathways for the flow of blood if one vessel becomes
obstructed.
An arterial anastomosis helps ensure that blood
will get to the capillaries of an organ to deliver oxygen
292 The Vascular System
and nutrients and to remove waste products. There
are arterial anastomoses, for example, between some
of the coronary arteries that supply blood to the
myocardium.
A venous anastomosis helps ensure that blood will
be able to return to the heart in order to be pumped
again. Venous anastomoses are most numerous among
the veins of the legs, where the possibility of obstruction
increases as a person gets older (see Box 13–2:
Disorders of Veins).
CAPILLARIES
Capillaries carry blood from arterioles to venules.
Their walls are only one cell in thickness; capillaries
are actually the extension of the endothelium, the simple
squamous lining, of arteries and veins (see Fig.
13–1). Some tissues do not have capillaries; these are
the epidermis, cartilage, and the lens and cornea of the
eye.
Most tissues, however, have extensive capillary networks.
The quantity or volume of capillary networks
in an organ reflects the metabolic activity of the organ.
The functioning of the kidneys, for example, depends
upon a good blood supply. Fig. 18–2 shows a vascular
cast of a kidney; you can see how dense the vessels are,
most of which are capillaries. In contrast, a tendon
such as the Achilles tendon at the heel or the patellar
tendon at the knee would have far fewer vessels,
because fibrous connective tissue is far less metabolically
active.
The Vascular System 293
Tunica externa
External elastic
lamina
Tunica
media
Internal elastic
lamina
Endothelium (lining)
Artery
Arteriole
Endothelial
cells
Smooth muscle
Precapillary
sphincter
Capillary
Blood flow
Venule
Vein
Valve
Tunica
intima
Tunica
externa
Tunica
media
Figure 13–1. Structure of
an artery, arteriole, capillary
network, venule, and vein.
See text for description.
QUESTION: What tissue is the
tunica media made of, and
how is this layer different in an
artery and in a vein?
Blood flow into capillary networks is regulated by
smooth muscle cells called precapillary sphincters,
found at the beginning of each network (see Fig. 13–1).
Precapillary sphincters are not regulated by the nervous
system but rather constrict or dilate depending on
the needs of the tissues. Because there is not enough
blood in the body to fill all of the capillaries at once,
precapillary sphincters are usually slightly constricted.
In an active tissue that requires more oxygen, such as
exercising muscle, the precapillary sphincters dilate to
increase blood flow. These automatic responses ensure
that blood, the volume of which is constant, will circulate
where it is needed most.
Some organs have another type of capillary called
sinusoids, which are larger and more permeable than
are other capillaries. The permeability of sinusoids
permits large substances such as proteins and blood
cells to enter or leave the blood. Sinusoids are found
in the red bone marrow and spleen, where blood cells
enter or leave the blood, and in organs such as the
294 The Vascular System
BOX 13–1 DISORDERS OF ARTERIES
The most common sites for aneurysm formation
are the cerebral arteries and the aorta, especially
the abdominal aorta. Rupture of a cerebral
aneurysm is a possible cause of a cerebrovascular
accident (CVA). Rupture of an aortic aneurysm is
life-threatening and requires immediate corrective
surgery. The damaged portion of the artery is
removed and replaced with a graft. Such surgery
may also be performed when an aneurysm is found
before it ruptures.
Atherosclerosis—this condition has been mentioned
previously; see Chapters 2 and 12.
Arteriosclerosis—although commonly called
“hardening of the arteries,” arteriosclerosis really
means that the arteries lose their elasticity, and their
walls become weakened. Arteries carry blood under
high pressure, so deterioration of their walls is part
of the aging process.
Aneurysm—a weak portion of an arterial wall
may bulge out, forming a sac or bubble called an
aneurysm. Arteriosclerosis is a possible cause, but
some aneurysms are congenital. An aneurysm may
be present for many years without any symptoms
and may only be discovered during diagnostic procedures
for some other purpose.
BOX 13–2 DISORDERS OF VEINS
to pool in the leg veins, stretching their walls. If the
veins become overly stretched, the valves within
them no longer close properly. These incompetent
valves no longer prevent backflow of blood, leading
to further pooling and even further stretching of
the walls of the veins. Varicose veins may cause discomfort
and cramping in the legs, or become even
more painful. Severe varicosities may be removed
surgically.
This condition may also develop during pregnancy,
when the enlarged uterus presses against
the iliac veins and slows blood flow into the inferior
vena cava. Varicose veins of the anal canal are called
hemorrhoids, which may also be a result of pregnancy
or of chronic constipation and straining to
defecate. Hemorrhoids that cause discomfort or
pain may also be removed surgically. Developments
in laser surgery have made this a simpler procedure
than it was in the past.
Phlebitis—inflammation of a vein. This condition
is most common in the veins of the legs, because
they are subjected to great pressure as the blood is
returned to the heart against the force of gravity.
Often no specific cause can be determined, but
advancing age, obesity, and blood disorders may
be predisposing factors.
If a superficial vein is affected, the area may be
tender or painful, but blood flow is usually maintained
because there are so many anastomoses
among these veins. Deep vein phlebitis is potentially
more serious, with the possibility of clot formation
(thrombophlebitis) and subsequent dislodging of
the clot to form an embolism.
Varicose veins—swollen and distended veins that
occur most often in the superficial veins of the legs.
This condition may develop in people who must sit
or stand in one place for long periods of time.
Without contraction of the leg muscles, blood tends
liver and pituitary gland, which produce and secrete
proteins into the blood.
EXCHANGES IN CAPILLARIES
Capillaries are the sites of exchanges of materials
between the blood and the tissue fluid surrounding
cells. Some of these substances move from the blood
to tissue fluid, and others move from tissue fluid to the
blood. The processes by which these substances are
exchanged are illustrated in Fig. 13–2.
Gases move by diffusion, that is, from their area of
greater concentration to their area of lesser concentration.
Oxygen, therefore, diffuses from the blood in
systemic capillaries to the tissue fluid, and carbon
dioxide diffuses from tissue fluid to the blood to be
brought to the lungs and exhaled.
Let us now look at the blood pressure as blood
enters capillaries from the arterioles. Blood pressure
here is about 30 to 35 mmHg, and the pressure of the
surrounding tissue fluid is much lower, about 2
mmHg. Because the capillary blood pressure is higher,
the process of filtration occurs, which forces plasma
and dissolved nutrients out of the capillaries and into
tissue fluid. This is how nutrients such as glucose,
amino acids, and vitamins are brought to cells.
Blood pressure decreases as blood reaches the
venous end of capillaries, but notice that proteins
such as albumin have remained in the blood. Albumin
contributes to the colloid osmotic pressure (COP)
of blood; this is an “attracting” pressure, a “pulling”
rather than a “pushing” pressure. At the venous end
of capillaries, the presence of albumin in the blood
pulls tissue fluid into the capillaries, which also brings
into the blood the waste products produced by
cells. The tissue fluid that returns to the blood
also helps maintain normal blood volume and blood
pressure.
The Vascular System 295
Precapillary sphincter Tissue fluid Cells Capillary
Tissue fluid -
Hydrostatic pressure
2 mmHg
COP 4 mmHg
CO2
CO2
CO2
O2
O2
O2
Plasma, glucose,
amino acids, vitamins
B. P. 33 mmHg
Albumin - COP 25 mmHg
B. P. 15 mmHg
Albumin - COP 25 mmHg
Tissue fluid,
waste products
VENOUS END
Outward forces 19
Inward forces 27
ARTERIAL END
Outward forces 37
Inward forces 27
Figure 13–2. Exchanges between blood in a systemic capillary and the surrounding tissue
fluid. Arrows depict the direction of movement. Filtration takes place at the arterial end
of the capillary. Osmosis takes place at the venous end. Gases are exchanged by diffusion.
QUESTION: Of all the pressures shown here, which one is the highest, and what process
does it bring about?
The amount of tissue fluid formed is slightly
greater than the amount returned to the capillaries. If
this were to continue, blood volume would be gradually
depleted. The excess tissue fluid, however, enters
lymph capillaries. Now called lymph, it will be
returned to the blood to be recycled again as plasma,
thus maintaining blood volume. This is discussed further
in Chapter 14.
PATHWAYS OF CIRCULATION
The two major pathways of circulation are pulmonary
and systemic. Pulmonary circulation begins at the
right ventricle, and systemic circulation begins at the
left ventricle. Hepatic portal circulation is a special
segment of systemic circulation that will be covered
separately. Fetal circulation involves pathways that are
present only before birth and will also be discussed
separately.
PULMONARY CIRCULATION
The right ventricle pumps blood into the pulmonary
artery (or trunk), which divides into the right and left
pulmonary arteries, one going to each lung. Within
the lungs each artery branches extensively into smaller
arteries and arterioles, then to capillaries. The pulmonary
capillaries surround the alveoli of the lungs; it
is here that exchanges of oxygen and carbon dioxide
take place. The capillaries unite to form venules,
which merge into veins, and finally into the two pulmonary
veins from each lung that return blood to the
left atrium. This oxygenated blood will then travel
through the systemic circulation. (Notice that the pulmonary
veins contain oxygenated blood; these are the
only veins that carry blood with a high oxygen content.
The blood in systemic veins has a low oxygen
content; it is systemic arteries that carry oxygenated
blood.)
SYSTEMIC CIRCULATION
The left ventricle pumps blood into the aorta, the
largest artery of the body. We will return to the aorta
and its branches in a moment, but first we will summarize
the rest of systemic circulation. The branches
of the aorta take blood into arterioles and capillary networks
throughout the body. Capillaries merge to form
venules and veins. The veins from the lower body take
blood to the inferior vena cava; veins from the upper
body take blood to the superior vena cava. These two
caval veins return blood to the right atrium. The major
arteries and veins are shown in Figs. 13–3 to 13–5, and
their functions are listed in Tables 13–1 and 13–2.
The aorta is a continuous vessel, but for the sake of
precise description it is divided into sections that are
named anatomically: ascending aorta, aortic arch, thoracic
aorta, and abdominal aorta. The ascending aorta
is the first inch that emerges from the top of the left
ventricle. The arch of the aorta curves posteriorly over
the heart and turns downward. The thoracic aorta
continues down through the chest cavity and through
the diaphragm. Below the level of the diaphragm, the
abdominal aorta continues to the level of the 4th lumbar
vertebra, where it divides into the two common
iliac arteries. Along its course, the aorta has many
branches through which blood travels to specific
organs and parts of the body.
The ascending aorta has only two branches: the
right and left coronary arteries, which supply blood to
the myocardium. This pathway of circulation was
described previously in Chapter 12.
The aortic arch has three branches that supply
blood to the head and arms: the brachiocephalic
artery, left common carotid artery, and left subclavian
artery. The brachiocephalic (literally, “arm-head”)
artery is very short and divides into the right common
carotid artery and right subclavian artery. The right
and left common carotid arteries extend into the neck,
where each divides into an internal carotid artery and
external carotid artery, which supply the head. The
right and left subclavian arteries are in the shoulders
behind the clavicles and continue into the arms. As the
artery enters another body area (it may not “branch,”
simply continue), its name changes: The subclavian
artery becomes the axillary artery, which becomes the
brachial artery. The branches of the carotid and subclavian
arteries are diagrammed in Figs. 13–3 and
13–5. As you look at these diagrams, keep in mind that
the name of the vessel often tells us where it is. The
facial artery, for example, is found in the face.
Some of the arteries in the head contribute to an
important arterial anastomosis, the circle of Willis
(or cerebral arterial circle), which is a “circle” of arteries
around the pituitary gland (Fig. 13–6). The circle
of Willis is formed by the right and left internal
carotid arteries and the basilar artery, which is the
union of the right and left vertebral arteries (branches
of the subclavian arteries). The brain is always active,
296 The Vascular System
(text continued on page 299)
The Vascular System 297
Occipital
Internal carotid
Vertebral
Brachiocephalic
Aortic arch
Maxillary
Facial
External carotid
Common carotid
Subclavian
Axillary
Pulmonary
Celiac
Left gastric
Hepatic
Splenic
Superior mesenteric
Abdominal aorta
Right common iliac
Internal iliac
External iliac
Femoral
Popliteal
Anterior tibial
Posterior tibial
Intercostal
Brachial
Renal
Gonadal
Inferior mesenteric
Radial
Ulnar
Deep palmar arch
Superficial palmar arch
Deep femoral
Figure 13–3. Systemic arteries. The aorta and its major branches are shown in anterior
view.
QUESTION: Can you find three arteries named after bones? After organs?
298 The Vascular System
Superior sagittal sinus
Inferior sagittal sinus
Straight sinus
Transverse sinus
Vertebral
External jugular
Internal jugular
Subclavian
Brachiocephalic
Pulmonary
Hepatic
Hepatic portal
Left gastric
Renal
Splenic
Inferior mesenteric
Internal iliac
Femoral
External iliac
Great saphenous
Popliteal
Small saphenous
Anterior tibial
Anterior facial
Superior vena cava
Axillary
Cephalic
Hemiazygos
Intercostal
Inferior vena cava
Brachial
Basilic
Gonadal
Superior mesenteric
Dorsal arch
Volar digital
Dorsal arch
Common iliac
Figure 13–4. Systemic veins shown in anterior view.
QUESTION: Can you find three veins with the same name as the accompanying artery?
even during sleep, and must have a constant flow of
blood to supply oxygen and remove waste products.
For this reason there are four vessels that bring blood
to the circle of Willis. From this anastomosis, several
paired arteries (the cerebral arteries) extend into the
brain itself.
The thoracic aorta and its branches supply the
chest wall and the organs within the thoracic cavity.
These vessels are listed in Table 13–1.
The abdominal aorta gives rise to arteries that supply
the abdominal wall and organs and to the common
iliac arteries, which continue into the legs. Notice in
Fig. 13–3 that the common iliac artery becomes the
external iliac artery, which becomes the femoral artery,
which becomes the popliteal artery; the same vessel
has different names based on location. These vessels
are also listed in Table 13–1 (see Box 13–3: Pulse
Sites).
The systemic veins drain blood from organs or
parts of the body and often parallel their correspond-
The Vascular System 299
Figure 13–5. Arteries and veins of the head and neck shown in right lateral view. Veins
are labeled on the left. Arteries are labeled on the right.
QUESTION: Which vein is the counterpart of the common carotid artery?
300 The Vascular System
Table 13–1 MAJOR SYSTEMIC ARTERIES
Branches of the Ascending Aorta and Aortic Arch
Artery Branch of Region supplied
Coronary a.
Brachiocephalic a.
Right common carotid a.
Right subclavian a.
Left common carotid a.
Left subclavian a.
External carotid a.
Superficial temporal a.
Internal carotid a.
Ophthalmic a.
Vertebral a.
Axillary a.
Brachial a.
Radial a.
Ulnar a.
Volar arch
Branches of the Thoracic Aorta
Artery Region Supplied
Intercostal a. (9 pairs)
Superior phrenic a.
Pericardial a.
Esophageal a.
Bronchial a.
Branches of the Abdominal Aorta
Artery Region Supplied
Inferior phrenic a.
Lumbar a.
Middle sacral a.
Celiac a.
Hepatic a.
Left gastric a.
Splenic a.
Superior mesenteric a.
Suprarenal a.
Renal a.
Inferior mesenteric a.
Ascending aorta
Aortic arch
Brachiocephalic a.
Brachiocephalic a.
Aortic arch
Aortic arch
Common carotid a.
External carotid a.
Common carotid a.
Internal carotid a.
Subclavian a.
Subclavian a.
Axillary a.
Brachial a.
Brachial a.
Radial and ulnar a.
• Myocardium
• Right arm and head
• Right side of head
• Right shoulder and arm
• Left side of head
• Left shoulder and arm
• Superficial head
• Scalp
• Brain (circle of Willis)
• Eye
• Cervical vertebrae and circle of Willis
• Armpit
• Upper arm
• Forearm
• Forearm
• Hand
• Skin, muscles, bones of trunk
• Diaphragm
• Pericardium
• Esophagus
• Bronchioles and connective tissue of the lungs
• Diaphragm
• Lumbar area of back
• Sacrum, coccyx, buttocks
• (see branches)
• Liver
• Stomach
• Spleen, pancreas
• Small intestine, part of colon
• Adrenal glands
• Kidneys
• Most of colon and rectum
ing arteries. The most important veins are diagrammed
in Fig. 13–4 and listed in Table 13–2.
HEPATIC PORTAL CIRCULATION
Hepatic portal circulation is a subdivision of systemic
circulation in which blood from the abdominal
digestive organs and spleen circulates through the
liver before returning to the heart.
Blood from the capillaries of the stomach, small
intestine, colon, pancreas, and spleen flows into two
large veins, the superior mesenteric vein and the
splenic vein, which unite to form the portal vein (Fig.
13–7). The portal vein takes blood into the liver,
where it branches extensively and empties blood into
the sinusoids, the capillaries of the liver (see also Fig.
16–6). From the sinusoids, blood flows into hepatic
veins, to the inferior vena cava and back to the right
atrium. Notice that in this pathway there are two sets
of capillaries, and keep in mind that it is in capillaries
that exchanges take place. Let us use some specific
examples to show the purpose and importance of portal
circulation.
Glucose from carbohydrate digestion is absorbed
into the capillaries of the small intestine; after a big
meal this may greatly increase the blood glucose level.
If this blood were to go directly back to the heart and
then circulate through the kidneys, some of the glucose
might be lost in urine. However, blood from the
small intestine passes first through the liver sinusoids,
and the liver cells remove the excess glucose and store
it as glycogen. The blood that returns to the heart will
then have a blood glucose level in the normal range.
Another example: Alcohol is absorbed into the capillaries
of the stomach. If it were to circulate directly
throughout the body, the alcohol would rapidly impair
the functioning of the brain. Portal circulation, however,
takes blood from the stomach to the liver, the
organ that can detoxify the alcohol and prevent its
detrimental effects on the brain. Of course, if alcohol
consumption continues, the blood alcohol level rises
faster than the liver’s capacity to detoxify, and the wellknown
signs of alcohol intoxication appear.
As you can see, this portal circulation pathway
enables the liver to modify the blood from the digestive
organs and spleen. Some nutrients may be stored
or changed, bilirubin from the spleen is excreted into
bile, and potential poisons are detoxified before the
blood returns to the heart and the rest of the body.
FETAL CIRCULATION
The fetus depends upon the mother for oxygen and
nutrients and for the removal of carbon dioxide and
The Vascular System 301
Table 13–1 MAJOR SYSTEMIC ARTERIES (Continued)
Branches of the Abdominal Aorta
Artery Region Supplied
Testicular or ovarian a.
Common iliac a.
Internal iliac a.
External iliac a.
Femoral a.
Popliteal a.
Anterior tibial a.
Dorsalis pedis
Plantar arches
Posterior tibial a.
Peroneal a.
Plantar arches
• Testes or ovaries
• The two large vessels that receive blood from the
abdominal aorta; each branches as follows:
• Bladder, rectum, reproductive organs
• Lower pelvis to leg
• Thigh
• Back of knee
• Front of lower leg
• Top of ankle and foot
• Foot
• Back of lower leg
• Medial lower leg
• Foot
302 The Vascular System
Table 13–2 MAJOR SYSTEMIC VEINS
Vein Vein Joined Region Drained
Head and Neck
Cranial venous sinuses
Internal jugular v.
External jugular v.
Subclavian v.
Brachiocephalic v.
Superior vena cava
Arm and Shoulder
Radial v.
Ulnar v.
Cephalic v.
Basilic v.
Brachial v.
Axillary v.
Subclavian v.
Trunk
Brachiocephalic v.
Azygos v.
Hepatic v.
Renal v.
Testicular or ovarian v.
Internal iliac v.
External iliac v.
Common iliac v.
Leg and Hip
Anterior and posterior tibial v.
Popliteal v.
Small saphenous v.
Great saphenous v.
Femoral v.
External iliac v.
Common iliac v.
Inferior vena cava
Internal jugular v.
Brachiocephalic v.
Subclavian v.
Brachiocephalic v.
Superior vena cava
Right atrium
Brachial v.
Brachial v.
Axillary v.
Axillary v.
Axillary v.
Subclavian v.
Brachiocephalic v.
Superior vena cava
Superior vena cava
Inferior vena cava
Inferior vena cava
Inferior vena cava
and left renal v.
Common iliac v.
Common iliac v.
Inferior vena cava
Popliteal v.
Femoral v.
Popliteal v.
Femoral v.
External iliac v.
Common iliac v.
Inferior vena cava
Right atrium
• Brain, including reabsorbed CSF
• Face and neck
• Superficial face and neck
• Shoulder
• Upper body
• Upper body
• Forearm and hand
• Forearm and hand
• Superficial arm and forearm
• Superficial upper arm
• Upper arm
• Armpit
• Shoulder
• Upper body
• Deep structures of chest and abdomen; links
inferior vena cava to superior vena cava
• Liver
• Kidney
• Testes or ovaries
• Rectum, bladder, reproductive organs
• Leg and abdominal wall
• Leg and lower abdomen
• Lower leg and foot
• Knee
• Superficial leg and foot
• Superficial foot, leg, and thigh
• Thigh
• Leg and abdominal wall
• Leg and lower abdomen
• Lower body
The Vascular System 303
other waste products. The site of exchange between
fetus and mother is the placenta, which contains fetal
and maternal blood vessels that are very close to one
another (see Figs. 13–8 and 21–5). The blood of the
fetus does not mix with the blood of the mother; substances
are exchanged by diffusion and active transport
mechanisms.
The fetus is connected to the placenta by the
umbilical cord, which contains two umbilical arteries
and one umbilical vein (see Fig. 13–8). The umbilical
arteries are branches of the fetal internal iliac arteries;
they carry blood from the fetus to the placenta. In the
placenta, carbon dioxide and waste products in the
fetal blood enter maternal circulation, and oxygen
Posterior communicating
Anterior cerebral
Circle of Willis
Anterior communicating
Posterior
cerebral
Middle
cerebral
Basilar
Internal
carotid
External carotid
Vertebral
Left
common carotid
Right
common carotid
ARTERIES
Anterior
cerebral
Anterior
communicating
Anterior
cerebral
Middle
cerebral
Internal
carotid
Posterior
cerebral
Posterior
communicating
Basilar
Vertebral
Spinal cord
Cerebellum
Medulla
Pons
Cerebrum
(temporal lobe)
Cerebrum
(frontal lobe)
Figure 13–6. Circle of Willis. This anastomosis is formed by the following arteries: internal
carotid, anterior communicating, posterior communicating, and basilar. The cerebral
arteries extend from the circle of Willis into the brain. The box shows these vessels in an
inferior view of the brain.
QUESTION: Why do so many vessels contribute to the circle of Willis?
and nutrients from the mother’s blood enter fetal
circulation.
The umbilical vein carries this oxygenated blood
from the placenta to the fetus. Within the body of the
fetus, the umbilical vein branches: One branch takes
some blood to the fetal liver, but most of the blood
passes through the ductus venosus to the inferior
vena cava, to the right atrium. After birth, when the
umbilical cord is cut, the remnants of these fetal vessels
constrict and become nonfunctional.
The other modifications of fetal circulation concern
the fetal heart and large arteries (also shown in
304 The Vascular System
Inferior vena cava
Hepatic vein
Liver
Portal vein
Superior
mesenteric V
Right colic V.
Ascending colon
Left gastric V.
Right gastric V.
Splenic V.
Spleen
Stomach
Pancreas
Left gastroepiploic V.
Inferior mesenteric V.
Left colic V.
Descending colon
Figure 13–7. Hepatic portal
circulation. Portions of
some of the digestive organs
have been removed to show
the veins that unite to form
the portal vein. See text for
description.
QUESTION: The blood in the
portal vein is going to what
organ? Where is the blood
coming from?
BOX 13–3 PULSE SITES
Popliteal—the popliteal artery at the back of the
knee.
Dorsalis pedis—the dorsalis pedis artery on the
top of the foot (commonly called the pedal pulse).
Pulse rate is, of course, the heart rate. However,
if the heart is beating weakly, a radial pulse may be
lower than an apical pulse (listening to the heart
itself with a stethoscope). This is called a pulse
deficit and indicates heart disease of some kind.
When taking a pulse, the careful observer also
notes the rhythm and force of the pulse. Abnormal
rhythms may reflect cardiac arrhythmias, and the
force of the pulse (strong or weak) is helpful in
assessing the general condition of the heart and
arteries.
A pulse is the heartbeat that is felt at an arterial site.
What is felt is not actually the force exerted by the
blood, but the force of ventricular contraction
transmitted through the walls of the arteries. This is
why pulses are not felt in veins; they are too far
from the heart for the force to be detectable.
The most commonly used pulse sites are:
Radial—the radial artery on the thumb side of the
wrist.
Carotid—the carotid artery lateral to the larynx in
the neck.
Temporal—the temporal artery just in front of the
ear.
Femoral—the femoral artery at the top of the
thigh.
Fig. 13–8). Because the fetal lungs are deflated and do
not provide for gas exchange, blood is shunted away
from the lungs and to the body. The foramen ovale is
an opening in the interatrial septum that permits some
blood to flow from the right atrium to the left atrium,
not, as usual, to the right ventricle. The blood that
does enter the right ventricle is pumped into the pulmonary
artery. The ductus arteriosus is a short vessel
that diverts most of the blood in the pulmonary
artery to the aorta, to the body. Both the foramen
ovale and the ductus arteriosus permit blood to bypass
the fetal lungs.
Just after birth, the baby breathes and expands its
lungs, which pulls more blood into the pulmonary circulation.
More blood then returns to the left atrium,
and a flap on the left side of the foramen ovale is
closed. The ductus arteriosus constricts, probably in
response to the higher oxygen content of the blood,
The Vascular System 305
Aortic arch
Ductus arteriosus
Pulmonary artery
Left atrium
Foramen
ovale
Right
atrium
Inferior vena cava
Aorta
Ductus venosus
Umbilical cord
Navel of fetus
Umbilical arteries
Umbilical vein
Placenta
Internal
iliac arteries
Maternal
blood vessels
Figure 13–8. Fetal circulation. Fetal heart and blood vessels are shown on the left.
Arrows depict the direction of blood flow. The placenta and umbilical blood vessels are
shown on the right. See text for description.
QUESTION: Find the foramen ovale in the fetal heart. Which way does blood flow through
it, and why?
and pulmonary circulation becomes fully functional
within a few days.
VELOCITY OF BLOOD FLOW
The velocity, or speed, with which blood flows differs
in the various parts of the vascular system. Velocity is
inversely related (meaning as one value goes up, the
other goes down) to the cross-sectional area of the
particular segment of the vascular system. Refer to
Fig. 13–9 as you read the following. The aorta receives
all the blood from the left ventricle, its cross-sectional
area is small, about 3 cm2 (1 sq. inch), and the blood
moves very rapidly, at least 30 cm per second (about 12
inches). Each time the aorta or any artery branches,
the total cross-sectional area becomes larger, and the
speed of blood flow decreases. Think of a river that
306 The Vascular System
4,000
3,000
2,000
1,000
30
20
10
120
100
80
60
40
20
0
Blood pressure
(mm Hg)
Pulse
pressure
Blood velocity
(cm/sec)
Cross-sectional
area (cm2)
Diastolic pressure
Systolic pressure
Aorta
Arteries
Arterioles
Capillaries
Venules
Veins
Vena Cavae
A
B
C
D
Figure 13–9. Characteristics of the vascular
system. (A) Schematic of the branching
of vessels. (B) Cross-sectional area in
square centimeters. (C) Blood velocity in
centimeters per second. (D) Systemic
blood pressure changes. Notice that systolic
and diastolic pressures become one
pressure in the capillaries.
QUESTION: Look at the cross-sectional
area and blood velocity. As area increases,
what happens to velocity? Where is velocity
slowest?
begins in a narrow bed and is flowing rapidly. If the
river bed widens, the water spreads out to fill it and
flows more slowly. If the river were to narrow again,
the water would flow faster. This is just what happens
in the vascular system.
The capillaries in total have the greatest crosssectional
area, and blood velocity there is slowest, less
than 0.1 cm per second. When capillaries unite to
form venules, and then veins, the cross-sectional area
decreases and blood flow speeds up.
Recall that it is in capillary networks that exchanges
of nutrients, wastes, and gases take place between the
blood and tissue fluid. The slow rate of blood flow in
capillaries permits sufficient time for these essential
exchanges. Think of a train slowing down (not actually
stopping) at stations to allow people to jump on
and off, then speeding up again to get to the next station.
The capillaries are the “stations” of the vascular
system.
The more rapid blood velocity in other vessels
makes circulation time quite short. This is the time it
takes for blood to go from the right ventricle to the
lungs, back to the heart to be pumped by the left ventricle
to the body, and return to the heart again.
Circulation time is about 1 minute or less, and ensures
an adequate exchange of gases.
BLOOD PRESSURE
Blood pressure is the force the blood exerts against
the walls of the blood vessels. Filtration in capillaries
depends upon blood pressure; filtration brings nutrients
to tissues, and as you will see in Chapter 18, is the
first step in the formation of urine. Blood pressure is
one of the “vital signs” often measured, and indeed a
normal blood pressure is essential to life.
The pumping of the ventricles creates blood pressure,
which is measured in mmHg (millimeters of
mercury). When a systemic blood pressure reading is
taken, two numbers are obtained: systolic and diastolic,
as in 110/70 mmHg. Systolic pressure is always
the higher of the two and represents the blood pressure
when the left ventricle is contracting. The lower
number is the diastolic pressure, when the left ventricle
is relaxed and does not exert force. Diastolic pressure
is maintained by the arteries and arterioles and is
discussed in a later section.
Systemic blood pressure is highest in the aorta,
which receives all of the blood pumped by the left ventricle.
As blood travels farther away from the heart,
blood pressure decreases (see Fig. 13–9). The brachial
artery is most often used to take a blood pressure reading;
here a normal systolic range is 90 to 120 mmHg,
and a normal diastolic range is 60 to 80 mmHg. In the
arterioles, blood pressure decreases further, and systolic
and diastolic pressures merge into one pressure.
At the arterial end of capillary networks, blood pressure
is about 30 to 35 mmHg, decreasing to 12 to 15
mmHg at the venous end of capillaries. This is high
enough to permit filtration but low enough to prevent
rupture of the capillaries. As blood flows through
veins, the pressure decreases further, and in the caval
veins, blood pressure approaches zero as blood enters
the right atrium.
The upper limit of the normal blood pressure range
is now 120/80 mmHg. The levels of 125 to 139/85 to
89 mmHg, once considered high-normal, are now
called “prehypertension,” that is, with the potential to
become even higher. A systemic blood pressure consistently
higher than the normal range is called hypertension
(see also Box 13–4: Hypertension). A lower
than normal blood pressure is called hypotension.
The regulation of systemic blood pressure is discussed
in a later section.
Pulmonary blood pressure is created by the right
ventricle, which has relatively thin walls and thus exerts
about one-sixth the force of the left ventricle. The
result is that pulmonary arterial pressure is always low:
20 to 25/8 to 10 mmHg, and in pulmonary capillaries
is lower still. This is important to prevent filtration in
pulmonary capillaries, which in turn prevents tissue
fluid from accumulating in the alveoli of the lungs.
MAINTENANCE OF SYSTEMIC
BLOOD PRESSURE
Because blood pressure is so important, many physiological
factors and processes interact to keep blood
pressure within normal limits:
1. Venous return—the amount of blood that returns
to the heart by way of the veins. Venous return
is important because the heart can pump only
the blood it receives. If venous return decreases,
the cardiac muscle fibers will not be stretched, the
force of ventricular systole will decrease (Starling’s
law), and blood pressure will decrease. This is what
might happen following a severe hemorrhage.
When the body is horizontal, venous return can
be maintained fairly easily, but when the body is
The Vascular System 307
vertical, gravity must be overcome to return blood
from the lower body to the heart. Three mechanisms
help promote venous return: constriction of
veins, the skeletal muscle pump, and the respiratory
pump.
Veins contain smooth muscle, which enables
them to constrict and force blood toward the heart;
the valves prevent backflow of blood. The second
mechanism is the skeletal muscle pump, which is
especially effective for the deep veins of the legs.
These veins are surrounded by skeletal muscles
that contract and relax during normal activities
such as walking. Contractions of the leg muscles
squeeze the veins to force blood toward the heart.
The third mechanism is the respiratory pump,
which affects veins that pass through the chest cavity.
The pressure changes of inhalation and exhalation
alternately expand and compress the veins, and
blood is returned to the heart.
2. Heart rate and force—in general, if heart rate and
force increase, blood pressure increases; this is
what happens during exercise. However, if the
heart is beating extremely rapidly, the ventricles
may not fill completely between beats, and cardiac
output and blood pressure will decrease.
3. Peripheral resistance—this term refers to the
resistance the vessels offer to the flow of blood.
The arteries and veins are usually slightly constricted,
which maintains normal diastolic blood
pressure. It may be helpful to think of the vessels
as the “container” for the blood. If a person’s body
has 5 liters of blood, the “container” must be
smaller in order for the blood to exert a pressure
against its walls. This is what normal vasoconstriction
does: It makes the container (the vessels)
smaller than the volume of blood so that the blood
will exert pressure even when the left ventricle is
relaxed.
308 The Vascular System
BOX 13–4 HYPERTENSION
trophy. This abnormal growth of the myocardium,
however, is not accompanied by a corresponding
growth in coronary capillaries, and the blood supply
of the left ventricle may not be adequate for all situations.
Exercise, for example, puts further
demands on the heart, and the person may experience
angina due to a lack of oxygen or a myocardial
infarction if there is a severe oxygen deficiency.
Although several different kinds of medications
(diuretics, vasodilators) are used to treat hypertension,
people with moderate hypertension may limit
their dependence on medications by following certain
guidelines:
1. Don’t smoke, because nicotine stimulates vasoconstriction,
which raises BP. Smoking also damages
arteries, contributing to arteriosclerosis.
2. Lose weight if overweight. A weight loss of as little
as 10 pounds can lower BP. A diet high in
fruits and vegetables may, for some people, contribute
to lower BP.
3. Cut salt intake in half. Although salt consumption
may not be the cause of hypertension,
reducing salt intake may help lower blood pressure
by decreasing blood volume.
4. Exercise on a regular basis. A moderate amount
of aerobic exercise (such as a half hour walk
every day) is beneficial for the entire cardiovascular
system and may also contribute to weight
loss.
Hypertension is high blood pressure, that is, a resting
systemic pressure consistently above the normal
range (90 to 120/60 to 80 mmHg). Clinicians now
consider 125 to 139/85 to 89 mmHg to be prehypertension.
A systolic reading of 140 to 159 mmHg
or a diastolic reading of 90 to 99 mmHg may be
called stage 1 hypertension, and a systolic reading
above 160 mmHg or a diastolic reading above 100
mmHg may be called stage 2 hypertension.
The term “essential hypertension” means that no
specific cause can be determined; most cases are in
this category. For some people, however, an overproduction
of renin by the kidneys is the cause
of their hypertension. Excess renin increases the
production of angiotensin II, which raises blood
pressure. Although hypertension often produces no
symptoms, the long-term consequences may be
very serious. Chronic hypertension has its greatest
effects on the arteries and on the heart.
Although the walls of arteries are strong, hypertension
weakens them and contributes to arteriosclerosis.
Such weakened arteries may rupture or
develop aneurysms, which may in turn lead to a
CVA or kidney damage.
Hypertension affects the heart because the left
ventricle must now pump blood against the higher
arterial pressure. The left ventricle works harder
and, like any other muscle, enlarges as more work is
demanded; this is called left ventricular hyper-
If more vasoconstriction occurs, blood pressure
will increase (the container has become even
smaller). This is what happens in a stress situation,
when greater vasoconstriction is brought about
by sympathetic impulses. If vasodilation occurs,
blood pressure will decrease (the container is
larger). After eating a large meal, for example, there
is extensive vasodilation in the digestive tract to
supply more oxygenated blood for digestive activities.
To keep blood pressure within the normal
range, vasoconstriction must, and does, occur elsewhere
in the body. This is why strenuous exercise
should be avoided right after eating; there is not
enough blood to completely supply oxygen to exercising
muscles and an active digestive tract at the
same time.
4. Elasticity of the large arteries—when the left
ventricle contracts, the blood that enters the large
arteries stretches their walls. The arterial walls are
elastic and absorb some of the force. When the left
ventricle relaxes, the arterial walls recoil or snap
back, which helps keep diastolic pressure within
the normal range. Normal elasticity, therefore,
lowers systolic pressure, raises diastolic pressure,
and maintains a normal pulse pressure. (Pulse pressure
is the difference between systolic and diastolic
pressure. The usual ratio of systolic to diastolic to
pulse pressure is approximately 3:2:1. For example,
with a blood pressure of 120/80 mmHg, the pulse
pressure is 40, and the ratio is 120:80:40, or 3:2:1.)
5. Viscosity of the blood—normal blood viscositydepends upon the presence of red blood cells and
plasma proteins, especially albumin. Having too
many red blood cells is rare but does occur in the
disorder called polycythemia vera and in people
who are heavy smokers. This will increase blood
viscosity and blood pressure.
A decreased number of red blood cells, as is seen
with severe anemia, or decreased albumin, as may
occur in liver disease or kidney disease, will
decrease blood viscosity and blood pressure. In
these situations, other mechanisms such as vasoconstriction
will maintain blood pressure as close to
normal as is possible.
6. Loss of blood—a small loss of blood, as when
donating a pint of blood, will cause a temporary
drop in blood pressure followed by rapid compensation
in the form of a more rapid heart rate and
greater vasoconstriction. After a severe hemorrhage,
however, these compensating mechanisms
may not be sufficient to maintain normal blood
pressure and blood flow to the brain. Although a
person may survive loss of 50% of the body’s total
blood, the possibility of brain damage increases as
more blood is lost and not rapidly replaced.
7. Hormones—several hormones have effects on
blood pressure. You may recall them from Chapters
10 and 12, but we will summarize them here and in
Fig. 13–10. The adrenal medulla secretes norepinephrine
and epinephrine in stress situations.
Norepinephrine stimulates vasoconstriction, which
raises blood pressure. Epinephrine also causes vasoconstriction,
and increases heart rate and force of
contraction, both of which increase blood pressure.
Antidiuretic hormone (ADH) is secreted by the
posterior pituitary gland when the water content of
the body decreases. ADH increases the reabsorption
of water by the kidneys to prevent further loss
of water in urine and a further decrease in blood
pressure.
Aldosterone, a hormone from the adrenal cortex,
has a similar effect on blood volume. When
blood pressure decreases, secretion of aldosterone
stimulates the reabsorption of Na ions by the kidneys.
Water follows sodium back to the blood,
which maintains blood volume to prevent a further
drop in blood pressure.
Atrial natriuretic peptide (ANP), secreted by the
atria of the heart, functions in opposition to aldosterone.
ANP increases the excretion of Na ions
and water by the kidneys, which decreases blood
volume and lowers blood pressure.
DISTRIBUTION OF BLOOD FLOW
An individual’s blood volume remains relatively constant
within the normal range appropriate to the size
of the person. Active tissues, however, require more
blood, that is, more oxygen, than do less active tissues.
As active tissues and organs receive a greater proportion
of the total blood flow, less active organs must
receive less, or blood pressure will decrease markedly.
As mentioned previously, precapillary sphincters
dilate in active tissues and constrict in less active ones.
The arterioles also constrict to reduce blood flow to
less active organs. This ensures that metabolically
active organs will receive enough oxygen to function
properly and that blood pressure for the body as a
whole will be maintained within normal limits.
An example will be helpful here; let us use the
body at rest and the body during exercise. Consult
Fig. 13–11 as you read the following. Resting cardiac
The Vascular System 309
output is approximately 5000 mL per minute. Exercise
cardiac output is three times that, about 15,000 mL
per minute. Keep in mind that the volume of blood is
the same in both cases, but that during exercise the
blood is being circulated more rapidly.
Compare the amounts of blood flowing to various
organs and tissues during exercise and at rest. During
exercise, the heart receives about three times as much
blood as it does when the body is at rest. The very
active skeletal muscles receive about ten times as much
blood. The skin, as an organ of heat loss, receives
about four times as much blood. Other organs, however,
can function adequately with less blood. Blood
flow is reduced to the digestive tract, to the kidneys,
and to other parts of the body such as bones.
When the exercise ceases, cardiac output will
gradually return to the resting level, as will blood flow
to the various organs. These changes in the distribution
of blood ensure sufficient oxygen for active tissues
and an appropriate blood pressure for the body as a
whole.
REGULATION OF BLOOD PRESSURE
The mechanisms that regulate systemic blood pressure
may be divided into two types: intrinsic mechanisms
and nervous mechanisms. The nervous mechanisms
involve the nervous system, and the intrinsic mechanisms
do not require nerve impulses.
INTRINSIC MECHANISMS
The term intrinsic means “within.” Intrinsic mechanisms
work because of the internal characteristics of
certain organs. The first such organ is the heart. When
310 The Vascular System
Adrenal gland
Pituitary
Heart
Norepinephrine
Epinephrine
Aldosterone
ADH
ANP
Increases
excretion of
Na+,
water follows
Kidney
Increases
reabsorption
of H2O
Increases
reabsorption of
Na+,
water follows
Increases rate
and force of
contraction
Vasoconstriction
Raises
B.P.
Lowers
B.P.
Figure 13–10. Hormones that affect blood pressure. See text for further description.
QUESTION: Which two hormones have opposite functions, and what are these functions?
venous return increases, cardiac muscle fibers are
stretched, and the ventricles pump more forcefully
(Starling’s law). Thus, cardiac output and blood pressure
increase. This is what happens during exercise,
when a higher blood pressure is needed. When exercise
ends and venous return decreases, the heart pumps
less forcefully, which helps return blood pressure to a
normal resting level.
The second intrinsic mechanism involves the kidneys.
When blood flow through the kidneys decreases,
the process of filtration decreases and less urine is
formed. This decrease in urinary output preserves
blood volume so that it does not decrease further.
Following severe hemorrhage or any other type of
dehydration, this is very important to maintain blood
pressure.
The kidneys are also involved in the reninangiotensin
mechanism. When blood pressure
decreases, the kidneys secrete the enzyme renin,
which initiates a series of reactions that result in the
formation of angiotensin II. These reactions are
described in Table 13–3 and depicted in Fig. 13–12.
Angiotensin II causes vasoconstriction and stimulates
secretion of aldosterone by the adrenal cortex, both of
which will increase blood pressure.
NERVOUS MECHANISMS
The medulla and the autonomic nervous system are
directly involved in the regulation of blood pressure.
The first of these nervous mechanisms concerns the
heart; this was described previously, so we will not
review it here but refer you to Chapter 12 and Fig.
12–7, as well as Fig. 13–13.
The Vascular System 311
Skeletal muscle
Blood distribution (mL/min)
Resting cardiac output
5,000 mL/min
Exercise cardiac output
15,000 mL/min
Heart Brain Skin GI tract Kidneys Rest of body
Resting
215 mL
% of
total
% of
total
Exercise
1,035 mL 645 mL 430 mL 1,205 mL 950 mL 515 mL
645 mL
10,710 mL 645 mL
1,635 mL
510 mL
510 mL
330 mL
4% 21% 13% 9% 24% 19% 10%
4.5% 71% 4.5% 11% 3.5% 3.5% 2%
Figure 13–11. Blood flow through various organs when the body is at rest and during
exercise. For each organ, the percentage of the total blood flow is given.
QUESTION: During exercise, which organs have the greatest increase in blood flow?
Which organs have the greatest decrease?
The second nervous mechanism involves peripheral
resistance, that is, the degree of constriction of the
arteries and arterioles and, to a lesser extent, the veins
(see Fig. 13–13). The medulla contains the vasomotor
center, which consists of a vasoconstrictor area and a
vasodilator area. The vasodilator area may depress the
vasoconstrictor area to bring about vasodilation,
which will decrease blood pressure. The vasoconstrictor
area may bring about more vasoconstriction by
way of the sympathetic division of the autonomic
nervous system.
Sympathetic vasoconstrictor fibers innervate the
smooth muscle of all arteries and veins, and several
impulses per second along these fibers maintain normal
vasoconstriction. More impulses per second bring
about greater vasoconstriction, and fewer impulses per
second cause vasodilation. The medulla receives the
information to make such changes from the pressoreceptors
in the carotid sinuses and the aortic sinus.
The inability to maintain normal blood pressure is one
aspect of circulatory shock (see Box 13–5: Circulatory
Shock).
312 The Vascular System
ANGIOTENSINOGEN
Liver
Lung and
vascular endothelium
CONVERTING ENZYME
ANGIOTENSIN I ANGIOTENSIN II
Vasoconstriction
Systemic
arteries
Increased
B. P.
Increased Na+ and
H2O reabsorption
ALDOSTERONE
Adrenal cortex
RENIN
Decreased
B. P.
Kidney
Figure 13–12. The renin-angiotensin mechanism. Begin at “Decreased B. P.” and see
Table 13–3 for numbered steps.
QUESTION: Where is renin produced? What are the functions of angiotensin II?
Table 13–3 THE RENIN-ANGIOTENSIN
MECHANISM
1. Decreased blood pressure stimulates the kidneys to
secrete renin.
2. Renin splits the plasma protein angiotensinogen (synthesized
by the liver) to angiotensin I.
3. Angiotensin I is converted to angiotensin II by an
enzyme (called converting enzyme) secreted by lung
tissue and vascular endothelium.
4. Angiotensin II:
• causes vasoconstriction
• stimulates the adrenal cortex to secrete aldosterone
313
Inhibit
vasomotor
center
Vasodilation
decreases
peripheral
resistance
Heart rate
slows,
decreases
cardiac output
B. P.
decreases to
normal range
B. P.
decreases
further
Stimulate
cardioinhibitory
center
Pressoreceptors in
carotid and aortic
sinuses stimulated
B. P.
increases
further
B. P.
increases to
normal
range
Vasoconstriction
increases
peripheral
resistance
Heart rate
and cardiac
output
increase
Stimulate
vasomotor
center
Stimulate
cardioaccelerator
center
Pressoreceptors in
carotid and aortic
sinuses inhibited
Figure 13–13. Nervous mechanisms that regulate blood pressure. See text for
description.
QUESTION: What kind of sensory information is used to make changes in BP, and
where are the receptors located?
AGING AND THE
VASCULAR SYSTEM
It is believed that the aging of blood vessels, especially
arteries, begins in childhood, although the effects are
not apparent for decades. The cholesterol deposits
of atherosclerosis are to be expected with advancing
age, with the most serious consequences in the coronary
arteries. A certain degree of arteriosclerosis is to
be expected, and average resting blood pressure may
increase, which further damages arterial walls.
Consequences include stroke and left-sided heart
failure.
The veins also deteriorate with age; their thin walls
weaken and stretch, making their valves incompetent.
This is most likely to occur in the veins of the legs;
their walls are subject to great pressure as blood is
returned to the heart against the force of gravity.
Varicose veins and phlebitis are more likely to occur
among elderly people.
SUMMARY
Although the vascular system does form passageways
for the blood, you can readily see that the blood vessels
are not simply pipes through which the blood
flows. The vessels are not passive tubes, but rather
active contributors to homeostasis. The arteries and
veins help maintain blood pressure, and the capillaries
provide sites for the exchanges of materials between
the blood and the tissues. Some very important sites of
exchange are discussed in the following chapters: the
lungs, the digestive tract, and the kidneys.
314 The Vascular System
BOX 13–5 CIRCULATORY SHOCK
Stages of Shock
Compensated shock—the responses by the body
maintain cardiac output. Following a small hemorrhage,
for example, the heart rate increases,
the blood vessels constrict, and the kidneys
decrease urinary output to conserve water. These
responses help preserve blood volume and maintain
blood pressure, cardiac output, and blood flow
to tissues.
Progressive shock—the state of shock leads to
more shock. Following a severe hemorrhage, cardiac
output decreases and the myocardium itself is
deprived of blood. The heart weakens, which further
decreases cardiac output. Arteries that are
deprived of their blood supply cannot remain constricted.
As the arteries dilate, venous return
decreases, which in turn decreases cardiac output.
Progressive shock is a series of such vicious cycles,
and medical intervention is required to restore cardiac
output to normal.
Irreversible shock—no amount of medical assistance
can restore cardiac output to normal. The
usual cause of death is that the heart has been damaged
too much to recover. A severe myocardial
infarction, massive hemorrhage, or septicemia may
all be fatal despite medical treatment.
Circulatory shock is any condition in which cardiac
output decreases to the extent that tissues are
deprived of oxygen and waste products accumulate.
Causes of Shock
Cardiogenic shock occurs most often after a
severe myocardial infarction but may also be the
result of ventricular fibrillation. In either case, the
heart is no longer an efficient pump, and cardiac
output decreases.
Hypovolemic shock is the result of decreased
blood volume, often due to severe hemorrhage.
Other possible causes are extreme sweating (heat
stroke) or extreme loss of water through the kidneys
(diuresis) or intestines (diarrhea). In these
situations, the heart simply does not have enough
blood to pump, and cardiac output decreases.
Anaphylactic shock, also in this category, is a massive
allergic reaction in which great amounts of
histamine increase capillary permeability and
vasodilation throughout the body. Much plasma is
then lost to tissue spaces, which decreases blood
volume, blood pressure, and cardiac output.
Septic shock is the result of septicemia, the
presence of bacteria in the blood. The bacteria and
damaged tissues release inflammatory chemicals
that cause vasodilation and extensive loss of plasma
into tissue spaces.
The vascular system consists of the arteries,
capillaries, and veins through which blood
travels.
Arteries (and arterioles) (see Fig. 13–1)
1. Carry blood from the heart to capillaries; three layers
in their walls.
2. Inner layer (tunica intima): simple squamous
epithelial tissue (endothelium), very smooth to prevent
abnormal blood clotting; secretes nitric oxide
(NO), a vasodilator.
3. Middle layer (tunica media): smooth muscle and
elastic connective tissue; contributes to maintenance
of diastolic blood pressure (BP).
4. Outer layer (tunica externa): fibrous connective tissue
to prevent rupture.
5. Constriction or dilation is regulated by the autonomic
nervous system.
Veins (and venules) (see Fig. 13–1)
1. Carry blood from capillaries to the heart; three layers
in walls.
2. Inner layer: endothelium folded into valves to prevent
the backflow of blood.
3. Middle layer: thin smooth muscle, because veins
are not as important in the maintenance of BP.
4. Outer layer: thin fibrous connective tissue because
veins do not carry blood under high pressure.
Anastomoses—connections between vessels
of the same type
1. Provide alternate pathways for blood flow if one
vessel is blocked.
2. Arterial anastomoses provide for blood flow to the
capillaries of an organ (e.g., circle of Willis to the
brain).
3. Venous anastomoses provide for return of blood to
the heart and are most numerous in veins of the
legs.
Capillaries (see Figs. 13–1 and 13–2)
1. Carry blood from arterioles to venules.
2. Walls are one cell thick (simple squamous epithelial
tissue) to permit exchanges between blood and tissue
fluid.
3. Oxygen and carbon dioxide are exchanged by
diffusion.
4. BP in capillaries brings nutrients to tissues and
forms tissue fluid in the process of filtration.
5. Albumin in the blood provides colloid osmotic
pressure, which pulls waste products and tissue fluid
into capillaries. The return of tissue fluid maintains
blood volume and BP.
6. Precapillary sphincters regulate blood flow into
capillary networks based on tissue needs; in active
tissues they dilate; in less active tissues they constrict.
7. Sinusoids are very permeable capillaries found in
the liver, spleen, pituitary gland, and red bone marrow
to permit proteins and blood cells to enter or
leave the blood.
Pathways of Circulation
1. Pulmonary: Right ventricle →pulmonary artery →
pulmonary capillaries (exchange of gases) → pulmonary
veins → left atrium.
2. Systemic: left ventricle → aorta → capillaries in
body tissues → superior and inferior caval veins →
right atrium (see Table 13–1 and Fig. 13–3 for systemic
arteries and Table 13–2 and Fig. 13–4 for systemic
veins).
3. Hepatic portal circulation: blood from the digestive
organs and spleen flows through the portal
vein to the liver before returning to the heart.
Purpose: the liver stores some nutrients or regulates
their blood levels and detoxifies potential poisons
before blood enters the rest of peripheral
circulation (see Fig. 13–7).
Fetal Circulation—the fetus depends on the
mother for oxygen and nutrients and for the
removal of waste products (see Fig. 13–8)
1. The placenta is the site of exchange between fetal
blood and maternal blood.
2. Umbilical arteries (two) carry blood from the fetus
to the placenta, where CO2 and waste products
enter maternal circulation.
3. The umbilical vein carries blood with O2 and nutrients
from the placenta to the fetus.
4. The umbilical vein branches; some blood
flows through the fetal liver; most blood flows
through the ductus venosus to the fetal inferior
vena cava.
5. The foramen ovale permits blood to flow from the
The Vascular System 315
STUDY OUTLINE
right atrium to the left atrium to bypass the fetal
lungs.
6. The ductus arteriosus permits blood to flow from
the pulmonary artery to the aorta to bypass the
fetal lungs.
7. These fetal structures become nonfunctional after
birth, when the umbilical cord is cut and breathing
takes place.
Velocity of Blood Flow (see Fig. 13–9)
1. Velocity is inversely related to the cross-sectional
area of a segment of the vascular system.
2. The total capillaries have the greatest crosssectional
area and slowest blood flow.
3. Slow flow in the capillaries is important to permit
sufficient time for exchange of gases, nutrients, and
wastes.
Blood Pressure (BP)—the force exerted by
the blood against the walls of the blood vessels
(Fig. 13–9)
1. BP is measured in mmHg: systolic/diastolic.
Systolic pressure occurs during ventricular contraction;
diastolic pressure occurs during ventricular
relaxation.
2. Normal range of systemic arterial BP: 90 to 120/60
to 80 mmHg.
3. BP in capillaries is 30 to 35 mmHg at the arterial
end and 12 to 15 mmHg at the venous end—high
enough to permit filtration but low enough to prevent
rupture of the capillaries.
4. BP decreases in the veins and approaches zero in
the caval veins.
5. Pulmonary BP is always low (the right ventricle
pumps with less force): 20 to 25/8 to 10 mmHg.
This low BP prevents filtration and accumulation
of tissue fluid in the alveoli.
Maintenance of Systemic BP
1. Venous return—the amount of blood that returns
to the heart. If venous return decreases, the heart
contracts less forcefully (Starling’s law) and BP
decreases. The mechanisms that maintain venous
return when the body is vertical are:
• Constriction of veins with the valves preventing
backflow of blood
• Skeletal muscle pump—contraction of skeletal
muscles, especially in the legs, squeezes the deep
veins
• Respiratory pump—the pressure changes of
inhalation and exhalation expand and compress
the veins in the chest cavity
2. Heart rate and force—if heart rate and force
increase, BP increases.
3. Peripheral resistance—the resistance of the arteries
and arterioles to the flow of blood. These vessels
are usually slightly constricted to maintain normal
diastolic BP. Greater vasoconstriction will increase
BP; vasodilation will decrease BP. In the body,
vasodilation in one area requires vasoconstriction
in another area to maintain normal BP.
4. Elasticity of the large arteries—ventricular systole
stretches the walls of large arteries, which recoil
during ventricular diastole. Normal elasticity lowers
systolic BP, raises diastolic BP, and maintains
normal pulse pressure.
5. Viscosity of blood—depends on RBCs and plasma
proteins, especially albumin. Severe anemia tends
to decrease BP. Deficiency of albumin as in liver or
kidney disease tends to decrease BP. In these cases,
compensation such as greater vasoconstriction will
keep BP close to normal.
6. Loss of blood—a small loss will be rapidly compensated
for by faster heart rate and greater vasoconstriction.
After severe hemorrhage, these
mechanisms may not be sufficient to maintain normal
BP.
7. Hormones—(see Fig. 13–10) (a) Norepinephrine
stimulates vasoconstriction, which raises BP; (b)
epinephrine increases cardiac output and raises BP;
(c) ADH increases water reabsorption by the kidneys,
which increases blood volume and BP; (d)
aldosterone increases reabsorption of Na ions by
the kidneys; water follows Na and increases blood
volume and BP; (e) ANP increases excretion of
Na ions and water by the kidneys, which decreases
blood volume and BP.
Distribution of Blood Flow
1. Metabolically active tissues require more oxygen,
and receive a greater proportion of the blood volume
as it circulates (see Fig. 13–11).
2. Blood flow is increased by the dilation of arterioles
and precapillary sphincters.
3. In less active tissues, arterioles and precapillary
sphincters constrict.
4. Organs receive sufficient oxygen, and BP for the
body is maintained within the normal range.
316 The Vascular System
Regulation of Blood Pressure—intrinsic
mechanisms and nervous mechanisms
Intrinsic Mechanisms
1. The heart—responds to increased venous return by
pumping more forcefully (Starling’s law), which
increases cardiac output and BP.
2. The kidneys—decreased blood flow decreases
filtration, which decreases urinary output to preserve
blood volume. Decreased BP stimulates the
kidneys to secrete renin, which initiates the reninangiotensin
mechanism (Table 13–3 and Fig.
13–12) that results in the formation of angiotensin
II, which causes vasoconstriction and stimulates
secretion of aldosterone.
Nervous Mechanisms (see Fig. 13–13)
1. Heart rate and force—see also Chapter 12.
2. Peripheral resistance—the medulla contains the
vasomotor center, which consists of a vasoconstrictor
area and a vasodilator area. The vasodilator area
brings about vasodilation by suppressing the vasoconstrictor
area. The vasoconstrictor area maintains
normal vasoconstriction by generating several
impulses per second along sympathetic vasoconstrictor
fibers to all arteries and veins. More
impulses per second increase vasoconstriction and
raise BP; fewer impulses per second bring about
vasodilation and a drop in BP.
The Vascular System 317
REVIEW QUESTIONS
1. Describe the structure of the three layers of the
walls of arteries, and state the function of each
layer. Describe the structural differences in these
layers in veins, and explain the reason for each difference.
(p. 292)
2. Describe the structure and purpose of anastomoses,
and give a specific example. (pp. 292–293)
3. Describe the structure of capillaries. State the
process by which each of the following is
exchanged between capillaries and tissue fluid:
nutrients, oxygen, waste products, and carbon
dioxide. (pp. 293–295)
4. State the part of the body supplied by each of the
following arteries: (pp. 297, 300)
a. Bronchial
b. Femoral
c. Hepatic
d. Brachial
e. Inferior mesenteric
f. Internal carotid
g. Subclavian
h. Intercostal
5. Describe the pathway of blood flow in hepatic portal
circulation. Use a specific example to explain the
purpose of portal circulation. (pp. 301, 304)
6. Begin at the right ventricle and describe the pathway
of pulmonary circulation. Explain the purpose
of this pathway. (p. 296)
7. Name the fetal structure with each of the following
functions: (pp. 303–305)
a. Permits blood to flow from the right atrium to
the left atrium
b. Carries blood from the placenta to the fetus
c. Permits blood to flow from the pulmonary
artery to the aorta
d. Carry blood from the fetus to the placenta
e. Carries blood from the umbilical vein to the
inferior vena cava
8. Describe the three mechanisms that promote
venous return when the body is vertical.
(pp. 307–308)
9. Explain how the normal elasticity of the large
arteries affects both systolic and diastolic blood
pressure. (p. 309)
10. Explain how Starling’s law of the heart is involved
in the maintenance of blood pressure. (p. 307)
11. Name two hormones involved in the maintenance
of blood pressure, and state the function of each.
(p. 309)
12. Describe two different ways the kidneys respond
to decreased blood flow and blood pressure.
(p. 311)
13. State two compensations that will maintain blood
pressure after a small loss of blood. (p. 309)
14. State the location of the vasomotor center and
name its two parts. Name the division of the
autonomic nervous system that carries impulses
to blood vessels. Which blood vessels? Which
tissue in these vessels? Explain why normal
vasoconstriction is important. Explain how
greater vasoconstriction is brought about. Explain
how vasodilation is brought about. How will
each of these changes affect blood pressure?
(pp. 312–313)
318 The Vascular System
FOR FURTHER THOUGHT
1. Some old textbooks used the term descending aorta.
Explain what is meant by that, and why it is not a
very good term. Explain why an aneurysm of the
aorta is quite likely to rupture sooner or later.
2. Renee, a nurse, is first on the scene of a car accident.
The driver has been thrown from the car, and
even from 15 feet away, Renee knows that a large
artery in the man’s leg has been severed. How does
she know this? What two things does she see?
Renee stops the bleeding, but the ambulance has
not arrived. She wants to assess the man’s condition
after he has lost so much blood. She cannot take a
blood pressure, but what other vital sign can be
helpful? Explain. If Renee could take a blood pressure
reading, what might it be? Might it be within
the normal range? Explain.
3. A friend tells you that her grandmother has a tendency
to develop blood clots in the veins of her
legs. Your friend fears that her grandmother will
have a stroke as a result. How would you explain
that a stroke from a clot there is not likely? Because
you are a good friend, you want to explain the serious
result that may occur. How would you do that?
4. Some people with hypertension take prescribed
diuretics. Some call these “water pills.” Is this an
accurate name? How can a diuretic help lower
blood pressure? What disadvantage does the use of
diuretics have?
5. Sinusoids are found in the liver and pituitary gland.
For each of these organs, name four specific large
molecules that enter the blood by way of sinusoids.
CHAPTER 14
The Lymphatic System
and Immunity
319
320