Human anatomy & physiology [Sixth edition ; International edition] 9780321204134, 0321204131, 9780805354638, 0805354638, 9781405814072, 1405814071, 080535462X, 0805354743, 0805716939

Table of contents :
Content: 1. The Human Body: An Orientation --
2. Chemistry Comes Alive --
3. Cells: The Living Units --
4. Tissue: The Living Fabric --
5. The Integumentary System --
6. Bones and Bone Tissue --
7. The Skeleton --
8. Joints --
9. Muscles and Muscle Tissue --
10. The Muscular System --
11. Fundamentals of the Nervous System and Nervous Tissue --
12. The Central Nervous System --
13. The Peripheral Nervous System and Reflex Activity --
14. The Autonomic Nervous System --
15. Neural Integration --
16. The Special Senses --
17. The Endocrine System --
18. Blood --
19. The Cardiovascular System: The Heart --
20. The Cardiovascular System: Blood Vessels --
21. The Lymphatic System --
22. Nonspecific Body Defenses and Immunity --
23. The Respiratory System --
24. The Digestive System --
25. Nutrition, Metabolism, and Body Temperature Regulation --
26. The Urinary System --
27. Fluid, Electrolyte, and Acid-Base Balance --
28. The Reproductive System --
29. Pregnancy and Human Development --
30. Heredity --
App. A. The Metric System --
App. B. The Genetic Code: Codon Sheet --
App. C. Amino Acid Structures --
App. D. Functional Groups in Organic Molecules --
App. E. Some Important Metabolic Pathways --
App. F. Periodic Table of the Elements --
App. G. Reference Values for Selected Blood and Urine Studies --
App. H. Answers to Multiple Choice, Matching, and Key Figure Questions --
Credits --
Glossary --
Index.

Citation preview

Human Anatomy &

Physiology

Sixth Edition

Elaine N. Marieb

Icon Identification

Guide

Word

Roots, Prefixes, Suffixes,

and Combining Forms

HOMEOSTATIC IMBALANCE Prefixes

and Combining Forms

Homcostatic imbalances are indicated by an orange symbol followed by a heading. The icon is used to reinforce the concept that disease is viewed as a loss of homeostasis, hence an imbalance in body

a-,

functioning.

ab- departing from;

an- absence or lack acardia, lack of a heart; anaerobic, in the ab-

sence of oxygen

away from abnormal,

departing from normal

acou- hearing acoustics, the science of sound ac-, aero-

extreme or

extremity-,

peak acrodermatitis, inflammation

of the skin of the extremities

ad- to or toward adorbital, toward the orbit

aden-, adeno- gland adeniform, resembling a gland in shape

Key questions

for selected figures address the

concepts or processes

depicted in the illustrations or in related topics covered earlier in the text.

Answers

same page

to these questions appear upside

down on

the

adren- toward the kidney adrenal gland, adjacent to the kidney aero- air aerobic respiration, oxygen-requiring metabolism af-

as the figure.

toward afferent neurons, which carry impulses to the central nervous system

agon-

contest

agonistic

and antagonistic muscles, which oppose

each other alb- white corpus albicans of the ovary, a white scar tissue

InterActive Physiology® icons in the Chapter

Summary

of

appropriate chapters refer the student to specific exercises on related InterActive Physiology® topics.

Thinking and Clinical Application Critical

Questions Thinking and Clinical Applications Questions at the end of every chapter are identified by a combined stethoscope and question

ailment- nourish alimentary canal, or digestive tract

one another alleles, alternative expressions of a gene amphi- on both sides; of both kinds amphibian, an organism capable of living in water and on land ana- apart, up, again anaphase of mitosis, when the chromosomes allel- of

separate

anastomos- come together arteriovenous anastomosis, a connection between an artery and a vein aneurysm a widening aortic aneurism, a weak spot that causes enlargement of the blood vessel

Critical

mark

icon.

angi- vessel angiitis, inflammation of a

lymph vessel

or blood vessel

angin- choked angina pectoris, a choked feeling in the chest due to dysfunction of the heart ant-, anti-

opposed

to-,

preventing or inhibiting anticoagulant, a sub-

stance that prevents blood coagulation ante- preceding; before antecubital, in front of the elbow aort- great artery aorta tip, extremity apex of the heart append- hang to appendicular skeleton aqua-, aque- water aqueous solutions

ap-, api-

i

arbor tree arbor vitae of the cerebellum, the treelike pattern of white

matter areola-

open space

areolar connective tissue, a loose connective

tissue

arrect-

upright

arrector pili muscles of the skin,

which make the

hairs stand erect arthr-, arthro- joint arthropathy,

any

joint disease

connection upper chambers of the heart auscult- hsten auscultatory method for measuring blood pressure artic- joint articular surfaces of bones, the points of atri- vestibule

atria,

aut-, auto- self autogenous, self-generated ax-, axi-,

axo- axis, axle axial skeleton, axis of vertebral

column

azyg- unpaired azygous vein, an unpaired vessel

baro- pressure baroreceptors for monitoring blood pressure basal base basal lamina of epithelial basement

membrane

two bicuspid, having two cusps bili- bile bilirubin, a bile pigment bio- life biology, the study of life and living organisms blast- bud or germ blastocyte, undifferentiated embryonic cell brachi- arm brachial plexus of peripheral nervous system supplies bi-

the

arm

brady- slow bradycardia, abnormally slow heart rate brev- short peroneus brevis, a short leg muscle

broncho- bronchus bronchospasm, spasmodic contraction of bronchial muscle bucco- cheek buccolabial, pertaining to the cheek and lip calor- heat calories, a measure of energy capill- hair blood

and lymph

capillaries

caput- head decapitate, remove the head

dys- difficult, faulty, painful dyspepsia, disturbed digestion

carcin- cancer carcinogen, a cancer-causing agent

ec-, ex-, ecto- out, outside,

harmful to the heart cameo- flesh trabeculae carneae, ridges of muscle in the ventricles

ectop-

lj carrot, 2)

stupor

1

)

carotene,

an orange pigment;

2) carotid

arteries in the neck, blockage causes fainting

down

cata-

caud-

cec- blind cele-

remove materials

ectopic pregnancy; ectopic focus for initiation of

displaced

edem- swelling edema, accumulation of water in body tissues away efferent nerve fibers, which carry impulses away from the

ef-

catabolism, chemical breakdown

central nervous system ejac- to shoot forth ejaculation of

caudal (directional term)

tail

excrete, to

heart contraction

of the heart

carot-

away from

horn the body

cardi, cardio- heart cardiotoxic,

cecum

abdominal

of large intestine, a blind-ended

celiac artery, in the

semen

embol- wedge embolus, an obstructive object traveling in the bloodstream

pouch

abdomen

em-

cephal- head cephalometer, an instrument for measuring the head

en-,

cerebro- brain, especially the cerebrum cerebrospinal, pertaining to

enceph- brain encephalitis, inflammation of the brain endo- within, inner endocytosis, taking particles into a cell entero- intestine enterologist, one who specializes in the study of

the brain and spinal cord

neck cervix of the uterus chiasm- crossing optic chiasma, where optic nerves cross cervic-, cervix

chole- bile cholesterol; cholecystokinin, a bile-secreting

chondr- cartilage chondrogenic, giving

;

coccy- cuckoo coccyx, which

is

excret separate excretory system

exo- outside, outer layer exophthalmos, an abnormal protrusion of the eye from the orbit

together in the center

beak- shaped

cochlea snail shell the cochlea of the inner

eso- within esophagus

eu- well euesthesia a normal state of the senses

small hair ciliated epithelium circum- around circumnuclear, surrounding the nucleus clavic- key clavicle, a "skeleton key"

common center,

epi- over, above epidermis, outer layer of skin

erythr- red erythema, redness of the skin erythrocyte, red blood cell

stain darkly

cili-

co-, con- together concentric,

extra-

ear,

which

is

body cavity commis- united gray commissure of the spinal cord connects the two columns of gray matter concha shell nasal conchae, coiled shelves of bone in the nasal cavity

fasci-, fascia-

contra- against contraceptive, agent preventing conception corn-, cornu- horn

stratum corneum, outer layer of the skin com-

posed of (horny) cells corona crown coronal suture of the skull corp- body corpse, corpus luteum, hormone-secreting body in the ovary cort- bark cortex, the outer layer of the brain, kidney, adrenal

ferr- iron

and lymph nodes intercostal, between the

both iron-storage proteins

whip flagellum, the tail blow, blown flatulence

of a

sperm

cell

bag, bellows hair follicle

folli-

fontan- fountain fontanels of the

foram- opening foramen

fetal skull

magnum

of the skull

foss- ditch fossa ovalis of the heart;

mandibular fossa of the skull

gam-, garnet- married, spouse gametes, the sex

cells

gangli- swelling, or knot dorsal root ganglia of the spinal nerves gastr-

stomach

gastrin, a

hormone

that influences gastric acid

gene beginning, origin genetics germin- grow germinal epithelium of the gonads

ribs

cryptomenorrhea, a condition in which menstrual are experienced but

no external

loss of blood occurs

gero-, geront- old

man

gerontology, the study of aging

gest- carried gestation, the period

from conception

to birth

glauc- gray glaucoma, which causes gradual blindness

cusp- pointed bicuspid, tricuspid valves of the heart cutic- skin cuticle of the nail

glom-

cyan- blue cyanosis, blue color of the skin due to lack of oxygen

glosso- tongue glossopathy, any disease of the tongue

cyst- sac, bladder cystitis,

inflammation of the urinary bladder

becoming inactive

decid- falling off deciduous (milk) teeth delta triangular deltoid muscle, roughly triangular in shape

glute- buttock gluteus

maximus,

largest

muscle of the buttock

gompho-

nail

self

gomphosis, the term applied to the joint between

tooth and jaw

dendrites, telodendria, both branches of a

neuron derm- skin dermis, deep layer of the skin desm- bond desmosome, which binds adjacent epithelial cells di- twice, double dimorphism, having two forms dia- through, between diaphragm, the wall through or between two areas

gon-, gono- seed, offspring gonads, the sex organs

gust- taste gustatory sense, the sense of taste

hapt- fasten, grasp hapten, a partial antigen

hema-, hemato-, hemo- blood hematocyst, a cyst containing blood hemi- half hemiglossal, pertaining to one-half of the tongue hepat- hver hepatitis, inflammation of the liver hetero- different or other heterosexuality, sexual desire for a person

dialys- separate, break apart

diastol-

from non-

gnost- knowing the gnostic sense, a sense of awareness of

den-, dent- tooth dentin of the tooth

ucts are

kidneys

carbohydrate molecules

de- undoing, reversal, loss, removal deactivation,

branch

ball glomeruli, clusters of capillaries in the

gluco-, glyco- gluconeogenesis, the production of glucose

cyt- cell cytology, the study of cells

tree,

an

secretion

crani- skull craniotomy, a skull operation

dendr-

cells of

fenestrae of the inner ear; fenestrated capillaries

transferrin, ferritin,

flagell-

glands,

hidden

body

extracellular, outside the

bundle, band superficial and deep fascia

window

fenestr-

flat-

symptoms

beyond

extrins- from the outside extrinsic regulation of the heart

a snail shell

crypt-

outside,

organism

coiled like

coel- hollow coelom, the ventral

cost- rib

inside encysted, enclosed in a cyst or capsule

intestinal disorders

hormone

rise to cartilage

chrom- colored chromosome, so named because they

in,

kidney

dialysis, in

which waste prod-

removed from the blood

stand apart

cardiac diastole, between successive contrac-

tions of the heart

draw ductus deferens which

gap the hiatus of the diaphragm, the opening through which the esophagus passes

hippo- horse hippocampus of the brain, shaped

diure- urinate diuretic, a drug that increases urine output dors- the back dorsal; dorsum,- dorsiflexion due-, duct lead,

of the opposite sex

hiat-

carries

epididymis into the urethra during ejaculation dura hard dura mater, tough outer meninx

sperm horn the

like a

seahorse

hirsut- hairy hirsutism, excessive body hair hist- tissue histology, the study of tissues

holo- whole holocrine glands, whose secretions are whole cells horn-, homo- same homeoplasia, formation of tissue similar to nor-

mal

tissue;

homocentric, having the same center

hormon- to excite hormones humor- a fluid humoral immunity, which

meningo- membrane meningitis, inflammation

which has no visible fibers hydr-, hydro- water dehydration, loss of body water

include the cell

hyper- excess hypertension, excessive tension

hypno- sleep hypnosis, a sleeplike state hypo- below, deficient hypodermic, beneath the skin hypokalemia, deficiency of potassium ;

uterus or

womb

uterus; hysterodynia, pain in the ile-

hysterectomy, removal of the

womb

intestine ileum, the last portion of the small intestine

intercal- insert intercalated discs, the

meso- middle mesoderm, middle germ layer meta- beyond, between, transition metatarsus, the part of the foot between the tarsus and the phalanges metro- uterus metroscope, instrument for examining the uterus micro- small microscope, an instrument used to make small objects appear larger mictur- urinate micturition, the act of voiding the bladder

mito- thread, filament mitochondria, small, filamentlike structures

im- not impermeable, not permitting passage, not permeable inter- between intercellular, between the cells

located in cells

mnem- memory amnesia

end membranes between ad-

jacent cardiac muscle cells

mono- single monospasm, spasm of a single limb morpho- form morphology, the study of form and

same

isothermal, equal, or same, temperature

juxta- near, close to juxtaglomerular apparatus, a cell cluster next to

the glomeruli in the kidneys

kernal nucleus

karyotype, the assemblage of the nuclear

chromosomes kera- born keratin, the water-repellent protein of the skin

thousand

to the lact-

narcotic, a

drug producing stupor or numbed

atrial natriuretic factor, a

sodium-regulating hormone

necro- death necrosis, tissue death

new neoplasm, an abnormal growth nephro- kidney nephritis, inflammation of the kidney neuro- nerve neurophysiology, the physiology of the nervous system noci- harmful nociceptors, receptors for pain nom- name innominate artery; innominate bone noto- back notochord, the embryonic structure that precedes the neo-

lacunae, the spaces occupied by cells of

and bone tissue

small plate

concentric lamellae, rings of bone matrix in

compact bone lamina layer, sheet basal lamina, part

of the epithelial

basement

membrane lat-

sodium

natrilip

gum

lacun- space, cavity, lake lamell-

numbness

sensations

kilocalories, equal to

milk lactose, milk sugar cartilage

multinuclear, having several nuclei

mural wall intramural ganglion, a nerve junction within an organ muta- change mutation, change in the base sequence of DNA myelo- spinal cord, marrow myeloblasts, cells of the bone marrow myo- muscle myocardium, heart muscle nano- dwarf nanometer, one billionth of a meter narco-

one thousand calories kin-, kines- move kinetic energy, the energy of motion labi-, labri- lip labial frenulum, the membrane which joins the kilo-

many

multi-

jugul- throat jugular veins, prominent vessels in the neck

karyo-

structure or

organisms

intra- within, inside intracellular, inside the cell iso- equal,

membranes

mer-, mero-, a part merocrine glands, the secretions of which do not

lating in the blood

hyal- clear hyaline cartilage,

hyster-, hystero-

of the

of the brain

involves antibodies circu-

vertebral

nucle-

wide latissimus

dorsi, a

broad muscle of the back

pit,

column

kernel, httle nut nucleus

nutri- feed, nourish nutrition

laten- hidden latent period of a muscle twitch

ob- before, against obstruction, impeding or blocking up

later- side lateral (directional term)

oculo- eye monocular, pertaining to one eye

leuko- white leukocyte, white blood

leva- raise, elevate levator labii superioris,

per

odonto- teeth orthodontist, one

cell

muscle that elevates up-

fat,

hpid

lipophage, a cell that has taken

up

fat in its

cytoplasm lith- stone cholelithiasis, gallstones

stratum lucidum, clear layer of the epidermis lumen, center of a hollow structure lut- yellow corpus luteum, a yellow, hormone-secreting structure in the ovary lymph water lymphatic circulation, return of clear fluid to the

oligo- few oligodendrocytes, neuroglial cells with few branches onco- a mass oncology, study of cancer oo- egg ocyte, precursor of female gamete ophthalmo- eye ophthalmology, the study of the eyes and related

disease

luci- clear

lumen

light

breast

mammary gland,

breast

mast- breast mastectomy, removal of a mammary gland mater mother dura mater, pia mater, membranes that envelop the

meat- passage external auditory meatus, the ear canal medi- middle medial (directional term) medull- marrow medulla, the middle portion of the kidney, adrenal

megameio-

orchi- testis cryptorchidism, failure of the testes to descend into the

scrotum org- hving organism

and lymph node

osm- smell anosmia, loss of sense of smell osmo- pushing osmosis osteo- bone osteodermia, bony formations in the skin oto- ear otoscope, a device for examining the ear ov-, ovi- egg ovum, oviduct oxy- oxygen oxygenation, the saturation of a substance with oxygen

meiosis, nuclear division that halves the

all,

universal panacea, a cure-all

nipple

papill-

dermal

papillae, projections of the

dermis into the

epidermal area

near paraphrenias, inflammation of tissues adjacent diaphragm pect-, pectus breast pectoralis major, a large chest muscle pelv- a basin pelvic girdle, which cradles the pelvic organs para-

beside,

to the

large megakaryocyte, large precursor cell of platelets less

orthopedic, correction of deformities of the

musculoskeletal system

pan-

brain

gland,

orb- circular orbicularis oculi, muscle that encircles the eye

ortho- straight, direct

bloodstream

macro- large macromolecule, large molecule macula spot macula lutea, yellow spot on the retina magn- large foramen magnum, largest opening of the skull mal- bad, abnormal malfunction, abnormal functioning of an organ

mamm-

specializes in proper position-

olfact- smell olfactory nerves

lip

lingua- tongue lingual tonsil, adjacent to the tongue lip-, lipo-

who

ing of the teeth in relation to each other

chromosome

number melan- black melanocytes, which secrete the black pigment melanin men-, menstru- month menses, the cyclic menstrual flow

peni- a

tail

penis; penile urethra

penna- a wing unipennate, bipennate muscles, whose a feathered appearance pent- five pentose, a 5-carbon sugar

fascicles

have

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6 Learning Activity

Sixth Edition:




Q

IV V7

9

•

ft

a

'

•

•Transitional

epithelium

Function: Stretches readily and permits distension of urinary organ by contained urine. Location: Lines the ureters, bladder, and part of the urethra.

•Basement

membrane

^ ^9

-

Photomicrograph:

Connective

%

tissue

Transitional epithelium lining of the bladder,

relaxed state (500x); note the bulbous, or rounded, appearance of the cells at the surface; these cells flatten and become elongated when the bladder is filled with urine.

FIGURE

4.2

volume

of urine to flow

the bladder,

(continued) Stratified epithelia

it

allows

(f).

through a tubelike organ. In to be stored.

more urine

initially, most have ducts, tubeconnections to the epithelial sheets.

sheet and, at least like

Endocrine Glands

Glandular Epithelia

A gland consists

of

Because endocrine glands eventually lose their

one or more

cells that

make and

secrete (export) a particular product. This product, called a secretion,

is

an aqueous (water-based)

but there is example, some glands release a lipid-

fluid that usually contains proteins,

variation

—

for

or steroid-rich secretion.

Secretion

is

an active

process; glandular cells obtain needed substances

from the blood and transform them chemically into a product that is then discharged from the cell. Notice that the term secretion can refer to both the gland's product and the process of making and releasing that product.

Glands are

classified as

endocrine ("internally

secreting") or exocrine ("externally secreting") de-

pending on where they release their product, and as unicellular ("one-celled") or multicellular ("manycelled") based on the relative cell number making up the gland. Unicellular glands are scattered within epithelial sheets.

By

contrast,

most multicellular

ep-

glands form by invagination (inward growth) or evagination (outward growth) from an epithelial ithelial

ducts, they are often called ductless glands.

They

produce hormones, regulatory, chemicals that they secrete by exocytosis directly into the extracellular space. From there the hormones enter the blood or lymphatic fluid and travel to specific target organs. Each hormone prompts its target organ(s) to respond in some characteristic way. For example, hormones produced by certain intestinal cells cause the pancreas to release

enzymes that help

digest food in the

digestive tract.

Endocrine glands are structurally diverse, so one description does not fit all. Although most endocrine glands are compact multicellular organs, some individual hormone-producing cells are scattered in the digestive tract mucosa and in the brain, giving rise to their collective description as the diffuse endocrine system. Their secretions are also varied, ranging from modified amino acids to peptides, glycoproteins, and steroids. Since not all endocrine glands are epithelial derivatives, we defer consideration of their structure and function to Chapter 16.

Chapter 4

Tubular secretory structure

Tissue:

The

125

Living Fabric

Alveolar secretory structure

Simple duct structure (duct does not branch) (a)

Simple tubular

(b)

intestinal

Simple branched

(c)

glands

Simple alveolar

(d)

Example: No important

tubular Example: stomach (gastric) glands

Example:

example

in

humans

Simple branched alveolar Example: sebaceous (oil)

glands

Compound duct structure (duct

branches)

(e)

Compound

tubular Example: Brunner's glands

(f)

of

Compound alveolar Example: mammary glands

(g)

Compound

tubuloalveolar Example: salivary glands

small intestine

Key:

j=

Surface epithelium

;

j=

Duct

Secretory epithelium

FIGURE

4.3

classified

according to duct type (simple or compound) and the structure of their

Types of multicellular exocrine glands.

Multicellular glands are

secretory units (tubular, alveolar, or tubuloalveolar).

Exocrine Glands Exocrine glands are endocrine glands, and

glycoprotein that dissolves in water far

more numerous than

many

of their products are

familiar. All exocrine glands secrete their

products onto body surfaces (skin) or into body cavities the unicellular glands directly (by exocytosis) and the multicellular glands via an epithelial-walled duct

—

that transports the secretion to the epithelial surface.

Exocrine glands are a diverse

lot.

They

include

mucous, sweat,

oil, and salivary glands, the liver (which secretes bile), the pancreas (which synthesizes digestive enzymes), and many others.

Unicellular Exocrine Glands

example

The only important

gland is the goblet cell. True to its name, a goblet cell is shaped like a goblet (a drinking glass with a stem). Goblet cells are

of a unicellular (or one-celled)

sprinkled in the epithelial linings of the in-

and respiratory

amid columnar cells with other functions (see Figure 4. 2d). In humans, all such glands produce mucin (mu'sin), a complex testinal

tracts

Once

dissolved,

when

mucin forms mucus,

ing that both protects

and lubricates

secreted.

a slimy coat-

surfaces.

Multicellular Exocrine Glands Compared to the unicellular glands, multicellular exocrine glands are structurally more complex. They have two basic parts: an epithelium-derived duct and a secretory unit consisting of secretory cells (acini). In all but the simplest glands, supportive connective tissue surrounds the secretory unit and supplies it with blood vessels and nerve fibers, and forms a fibrous capsule that extends into the gland proper and divides the gland into lobes. Structural classification. On the basis of their duct structures, multicellular exocrine glands are either simple or compound (Figure 4.3). Simple glands have an unbranched duct, whereas compound glands have a branched duct. The glands are further categorized by their secretory units as (1) tubular if the secretory cells form tubes; (2) alveolar

126

Unit

I

Organization of the Body

Which of the gland types

illustrated

highest rate of cellular mitosis?

would have the

Secretory cells of holocrine glands (hol'o-krin)

Why?

accumulate their products within them until they rupture. (They are replaced by the division of underlying cells.) Because holocrine gland secretions include the synthesized product plus dead cell frag-

0

ments

=

[holos

you could say that

all),

"die for their cause." Sebaceous

their cells

glands of the skin are the only true example of holocrine glands (oil)

(Figure 4.4b).

Although apocrine (ap'o-krin) glands are nitely present in other animals, there

troversy over whether Secretory

humans have

defi-

some con-

is

this third gland

type. Like holocrine glands, apocrine glands accu-

vesicles

mulate their products, but in this case only just beneath the free surface. Eventually, the apex of the cell pinches off [apo = from, off), releasing the secre-

amount

tory granules and a small cell repairs its

damage and the process

and again. The best

possibility in

lease of lipid droplets

most

Secretory cell fragments

of cytoplasm.

The

repeats again

humans

is

the

re-

mammary glands, but mammary glands as mero-

by the

histologists classify

crine glands because this

the

is

means by which milk

proteins are secreted.

Connective Tissue Connective tissue is found everywhere in the body. the most abundant and widely distributed of the primary tissues, but its amount in particular organs It is

varies. For

example, skin consists primarily of con-

nective tissue, while the brain contains very (b)

There are four main classes several subclasses.

Chief modes of secretion in human exocrine glands, (a) Merocrine glands secrete their products by exocytosis. (b) In holocrine glands, the entire secretory cell ruptures, releasing secretions and dead cell

FIGURE

4.4

tive tissue

and

fragments.

(al-ve'o-lar)

if

the secretory cells form small, flask-

like sacs {alveolus

= "small hollow

cavity");

and

they have both types of secre(3) tory units. Note that the term acinar (as'i-nar "berrylike") is used interchangeably with alveolar. tubuloalveolar

if

;

Modes

classes are

proper (which includes (2)

(

1

)

and

connec-

and the fibrous (3) bone tissue,

fat

cartilage,

blood.

Connective tissue does much more than just connect body parts; it has majiy forms and functions. Its major functions include (1) binding and support, (2) protection, (3) insulation, and as blood, (4) transportation of substances within the body. For example, bone and cartilage support and protect body organs by providing the hard underpinnings of the skeleton; fat cushions insulate and protect body organs and provide reserve energy fuel.

of secretion. Multicellular exocrine glands

can also be described functionally. Most are merocrine glands (mer'o-krin), which secrete their products by secrete their products in different ways, so they

exocytosis as they are produced. The secretory cells are not altered in any way. The pancreas, most sweat glands,

(4)

of connective tissue

The main

tissue of ligaments),

little.

and salivary glands belong

to this class

(Figure 4.4a).

jet/} Sjjdo

paoejddj eq 0} SAeq psjajoas

asneoaq 'pue/6 au/joo/ou

3tjj_

Characteristics

of Connective Tissue Despite their

many and

diverse functions in the

body, connective tissues have ties that set 1.

I pue paiuduj6ejj dje

Common

them

Common

some common

proper-

apart from other primary tissues:

origin. All connective tissues arise

from mesenchyme (an embryonic tissue) and hence have a common kinship (Figure 4.5).

)

Chapter 4

Tissue:

The

127

Living Fabric

Common Mesenchyme

embryonic origin:

Hematopoietic stem

Blood

cells*

cell

(and macrophages)

O

,

ooc

Class of connective Connective tissue proper

tissue resulting:

Subclasses:

1

.

Loose connective

Osseous (bone)

Cartilage

1.

Hyaline

1.

cartilage

tissue

Compact bone

Blood

*

Blood cell formation

and differentiation are quite complex.

Types:

Areolar

2. Fibrocartilage

2.

Adipose Reticular

Spongy

Details are provided

(cancellous)

in

Chapter

1 7.

bone

3. Elastic

cartilage 2.

Dense connective tissue

Types:

Regular Irregular

Elastic

FIGURE

4.5

Major classes of connective tissue.

All

these classes arise

from the same embryonic tissue type (mesenchyme).

2.

the entire

gamut

of vascularity. Cartilage

is

avascu-

dense connective tissue is poorly vascularized; and the other types of connective tissue have a rich supply of blood vessels.

lar;

Whereas all other primary composed mainly of cells, connective tissues are largely nonliving extracellular matrix (ma'triks; "womb"), which separates, often widely the

3.

The

Degrees of vascularity. Connective tissues run

Extracellular matrix.

tissues are

Because of its matrix, connecwithstand great tension, and endure abuses, such as physical trauma and abrasion, that no other tissue would be able to tolerate.

living cells of the tissue.

tive tissue is able to bear weight,

Structural Elements

of Connective Tissue Connective tissues have three main elements: ground substance, fibers, and cells. Ground substance and fibers make up the extracellular matrix. (Note that some authors use the term matrix to indicate the ground substance only.

properties of the cells and the composition

and arrangement of extracellular matrix elements vary tremendously. The result is an amazing diversity of connective tissues, each adapted to perform its specific function in the body. For example, the matrix can be delicate and fragile to form a soft "packing" around an organ, or it can form "ropes" (tendons and ligaments) of incredible strength. Nonetheless, connective tissues have a common structural plan, and we use areolar (ah-re'o-lar) connective tissue as our prototype, or model, for this group of tissues (see Figure 4.7). All other subclasses are simply variants of this common tissue type.

Ground Substance Ground substance fills

the unstructured material that the space between the cells and contains the

fibers. It is

is

composed

of interstitial (tissue) fluid, cell

adhesion proteins, and proteoglycans (pro"te-ogli'kanz). Cell adhesion proteins (fibronectin, laminin, and others) serve mainly as a connective tissue glue that allows connective tissue cells to

128

Unit

Organization of the Body

I

attach themselves to matrix elements. The proteoglycans consist of a protein core to which gly-

cosaminoglycans lgli"kos-ah-me"no-gli'kanz) (GAGs) are attached. tively

The

strandlike

GAGs

are large, nega-

charged polysaccharides that stick out from

the core protein like the fibers of a bottle brush (Fig-

ure 4.6). Important examples of GAGs in connective tissues include chondroitin and keratan sulfates and hyaluronic (hi"ah-lu-ron'ik) acid. The proteoglycans tend to form huge aggregates (often attached to a hyaluronic acid molecule!. The GAGs intertwine

and trap water, forming

from

a substance that varies

a fluid to a viscous gel. In general, the higher its

GAG

content, the

stance

more viscous the ground sub-

is.

The ground substance holds

large

amounts of or medium,

and functions as a molecular sieve, through which nutrients and other dissolved substances can diffuse between the blood capillaries and the cells. The fibers embedded in the ground subfluid

stance

make

it

less pliable

and impede diffusion

somewhat. (a)

Fibers

The

fibers

of connective tissue provide support.

Three types of

fibers are found in connective tissue matrix: collagen, elastic, and reticular fibers. Of

these, collagen fibers are

by

far the strongest

and

most abundant. Collagen fibers are constructed primarily of the Collagen molecules are

fibrous protein collagen.

secreted into the extracellular space,

where they

as-

semble

spontaneously into cross-linked fibers, which in turn are bundled together into the thick collagen fibers seen with a microscope. Collagen fibers are extremely tough and provide high tensile strength (that

the ability to resist longitudinal stress' to the matrix. Indeed, stress tests show that collagen fibers are stronger than steel fibers of the same size! When fresh, they have a glistening is,

white appearance; they are therefore also called white fibers. Elastic fibers are long, thin fibers that

Keratan sulfate

form

branching networks in the extracellular matrix. These fibers contain a rubberlike protein, elastin, that allows

them

to stretch

and

Chondroitin sulfate

Core protein

recoil like rubber

uronic acid

bands. Connective tissue can stretch only so much before its thick, ropelike collagen fibers become taut.

Then, when the tension lets up, elastic fibers snap the connective tissue back to its normal length and shape. Elastic fibers are found where greater elasticity is needed, for example, in the skin, lungs, and biood vessel walls. Because fresh elastic fibers appear yellow they are sometimes called yellow fibers. Reticular fibers are fine collagenous fibers (with a slightly different chemistry and form) and are continuous with collagen fibers. They branch

Link protein (b)

FIGURE

4.6

cartilage, (a)

Proteoglycan structure

An

in

bovine

electron micrograph of a proteoglycan

aggregate, (b) A schematic drawing of the same structure. Keratan sulfate and chondroitin sulfate are linked to core protein molecules, which attach to a long hyaluronic acid

molecule with the aid of

a link protein.

Chapter 4

Tissue:

The

129

Living Fabric

Areolar connective tissue: A prototype (model) connective tissue. This tissue underlies epithelia and surrounds capillaries. Note the various cell types and the three classes of fibers (collagen, reticular, elastic) embedded in the ground substance. (See Figure 4.8b for a less idealized version.)

FIGURE

4.7

forming delicate networks [reticul = network) that surround small blood vessels and extensively,

support the soft tissue of organs. They are particuabundant where connective tissue abuts other tissue types, for example, in the basement membrane of epithelial tissues, and around capillaries, where they form fuzzy "nets" that allow more "give" than the larger collagen fibers. larly

Cells

Each major class of connective tissue has a fundamental cell type that exists in immature and mature forms (see Figure 4.5). The undifferentiated cells, indicated by the suffix blast (literally, "bud," or

meaning "forming"), are actively mithat secrete the ground substance and

"sprout," but totic cells

the fibers characteristic of their particular matrix. The primary blast cell types by connective tissue class are (1) connective tissue proper: fibroblast; (2)

chondroblast (kon'dro-blast")

cartilage:

teoblast etic

(

stem

os 'te-o -blast"); and

(4)

;

blood:

(3)

bone: os-

hematopoi-

is

injured, they can easily revert to their

more

and regenerate the matrix. (The blood-forming hematopoietic stem cell found in bone marrow is always actively mitotic.) Additionally, connective tissue is home to an assortment of other cell types, such as nutrient-storing fat cells and mobile cells that migrate into the connective tissue matrix from the bloodstream. The latter include defensive white blood cells (neutrophils, eosinophils, lymphocytes) and other cell types concerned with tissue response to injury, such as mast cells, macrophages (mak'ro-faj-es), and antibodyproducing plasma cells. This wide variety of cells is active state to repair

particularly obvious in our prototype, areolar con-

nective tissue (Figure 4.7). All of these accessory cell types are described in later chapters,

but mast

cells

and macrophages are

so important to overall body defense that they deserve a brief mention here. The oval mast cells typically cluster along blood vessels.

These

cells act as

sensitive sentinels to detect foreign substances

(e.g.,

and initiate local inflammatory responses against them. In the mast cell cytoplasm are conspicuous secretory granules (mast = "stuffed full

bacteria, fungi)

cell.

Once they synthesize the matrix, the blast cells assume their less active, mature mode, indicated by the suffix cyte (see Figure 4.5). The mature cells maintain the health of the matrix. However,

matrix

if

the

of granules") containing several chemicals that

me-

diate inflammation, especially in severe allergies.

)

130

Unit

Organization of the Body

I

(1) heparin (hep'ah-rin), an anticoagulant chemical that prevents blood clotting when free in the bloodstream (but in human mast cells it appears to bind to and regulate the action of other mast cell chemicals); (2) histamine (his'tah-men), a substance that makes capillaries leaky; and (3) proteases (protein-degrading enzymes).

These include

Macrophages [macro = shaped

large, irregularly

large;

phago =

cells that avidly

eat) are

phagocytize

a broad variety of foreign materials, ranging

from

for-

eign molecules to entire bacteria to dust particles.

These "big eaters" also dispose of dead tissue cells, and they are central actors in the immune system. In connective tissues, they

may

nective tissue fibers (fixed)

be attached to conor may migrate freely

through the matrix.

Macrophages

are peppered throughout loose con-

nective tissue, bone marrow, and lymphatic tissue.

Those

in certain sites are given specific names; for example, those in loose connective tissue are called histiocytes (his'te-o-sitz"). Some macrophages have selective appetites; for example, those of the spleen primarily dispose of aging red blood cells, but they will not turn down other "delicacies" that come their way.

dense lage,

irregular,

and blood,

and elastic). Except for bone, cartimature connective tissues belong

all

to this class.

Areolar connecAreolar Connective Tissue tive tissue, as you may have guessed, is special. Its functions, shared by some but not all connective tissues, include 1 supporting and binding other tissues (the job of the fibers); (2) holding body fluids (the ground substance's role); (3) defending against infection (via the activity of white blood cells and (

macrophages);

)

(4)

storing nutrients as fat (in fat

cells) (Figure 4.8b).

branching cells that appear spindle shaped in profile, predominate, but numerous macrophages are also seen and present a formidable barrier to invading microorganisms. Fat cells appear singly or in small clusters, and occasional mast cells are identified easily by the large, darkly stained cytoplasmic granules that often obscure their nuclei. Other cell types are scattered throughFibroblasts,

flat,

out.

The most obvious

structural feature of this tissue

the loose arrangement of its fibers,- hence, its classification as a loose connective tissue is fitting. The

is

occupied by ground substance, appears to be empty space when viewed through the microscope; in fact, the Latin term areola means "a small open space." Because of its loose nature, areolar connective tissue provides a reservoir of water and salts for surrounding body tissues, always holding approximately as much fluid as there is in the entire bloodstream. Essentially all body cells obtain their nutrients from and release their wastes into this "tissue fluid." However, its high content of hyaluronic acid makes the ground substance quite viscous, like molasses, which may hinder the movement of cells through it. Some white blood cells, which protect the body from disease-causing microorganisms, secrete rest of the matrix,

Types of Connective Tissue As noted,

all

living cells

classes of connective tissue consist of

surrounded by a matrix. Their major

ferences reflect cell type, relative type, and of fibers.

The connective

dif-

amount

tissues described in this

Mature connecembryonic tissue,

section are illustrated in Figure 4.8. tive tissues arise from a common which we describe here as well.

Embryonic Connective Tissue: Mesenchyme Mesenchyme (mes'en-kim) is the first definitive tissue

formed from the mesoderm germ layer

p. 147). Mesenchyme shaped mesenchymal cells and

ure 4.13,

stance containing fine

is

composed

(see Fig-

of star-

a fluid ground sub-

fibrils (Figure 4.8a). It arises

during the early weeks of embryonic development and eventually differentiates (specializes) into all other connective tissues. However, some mesenchymal cells remain and provide a source of new cells in mature connective tissues.

Mucous connective tissue is a temporary tissue derived from mesenchyme and similar to it. Wharton 's

jelly,

of the fetus, is bryonic tissue.

which supports the umbilical cord the best example of this scant em-

Connective Tissue Proper Connective tissue proper has two subclasses: the loose connective tissues (areolar, adipose, and reticular) and dense connective tissues (dense regular,

the

enzyme hyaluronidase,

to liquefy the

ground sub-

stance and ease their passage. (Unhappily,

some

po-

harmful bacteria have the same ability.) When a body region is inflamed, the areolar tissue in the area soaks up excess fluids like a sponge, and the affected area swells and becomes puffy, a condition tentially

called

edema

(e-de'mah).

most widely disbody and it serves as a kind of universal packing material between other tissues. It binds body parts together while allowing them to move freely over one another; wraps small blood vessels and nerves; surrounds glands; and forms the subcutaneous tissue, which cushions and attaches the skin to underlying strucAreolar connective tissue

is

the

tributed connective tissue in the

tures. It is present in all

mucous membranes

lamina propria. (Mucous membranes ties open to the exterior.

line

as the

body

cavi-

Chapter 4

(a)

Tissue:

The

Living Fabric

131

Embryonic connective tissue: mesenchyme

Description: Embryonic connective tissue; gel-like

ground substance containing

Mesenchymal

fibers;

star-shaped mesenchymal

cells.

Function: Gives

other connective

cell

Ground rise to all

substance

tissue types.

Location: Primarily

in

embryo.

Fibers

Photomicrograph: Mesenchymal

tissue,

an embryonic

connective tissue (400x); the clear-appearing background

is

the fluid ground substance of the matrix; notice the fine,

sparse

(b)

fibers.

Connective tissue proper: loose connective tissue, areolar

Description: Gel-like matrix with types; cells: fibroblasts, cells,

all

three fiber

macrophages, mast

and some white blood

Elastic

cells.

fibers

Function: Wraps and cushions organs; its macrophages phagocytize bacteria; plays important role

in

conveys tissue

inflammation; holds and

Collagen

fluid.

fibers

Location: Widely distributed under epithelia forms lamina propria of mucous membranes; packages organs; surrounds

of body, e.g.

Fibroblast nuclei

capillaries.

Epithelium

Lamina

Photomicrograph: Areolar connective body (400x).

propria

FIGURE

tissue of the

4.8

Connective tissues. Embryonic connective

connective tissue proper

(b).

tissue (a)

and

tissue, a soft

packaging

132

(c)

Unit

I

Organization of the Body

Connective tissue proper: loose connective tissue, adipose

Description: Matrix as in areolar, but very sparse; closely packed adipocytes, or fat cells,

have nucleus pushed

to the side

by large

fat

droplet.

Function: Provides reserve food fuel; insulates against heat loss; supports and protects organs.

Location: Under eyeballs; within

skin;

around kidneys and

abdomen;

in

breasts.

Nuclei of fat cells

Vacuole containing fat droplet

Photomicrograph: Adipose

tissue from the

subcutaneous

layer under the skin (600x).

FIGURE

4.8

Adipose

(continued)

Connective tissues. Connective

Adipose tissue (ad'i-pos) is similar to areolar tissue in structure and function but its nutrient- storing ability is much greater. Consequently,

(Fat) Tissue

adipocytes

(ad'i-po-sitz),

commonly

predominate and account for 90% of this tissue's mass. The matrix is scanty and the cells are packed closely together, giving a chicken wire appearance to the tissue. A glistening oil droplet (almost pure neutral fat) occupies most of a fat cell's volume and displaces the nucleus to one side so that only a thin rim of surrounding cytoplasm is seen (Figure 4.8c). Mature adipocytes are called adipose or fat cells,

among

As they take up they become plumper or more wrin-

the largest cells in the body.

or release

fat,

kled looking, respectively.

Adipose tissue is richly vascularized, indicating high metabolic activity. Without the fat stores in our adipose tissue, we could not live for more than a few days without eating. Adipose tissue is certainly abundant: It constitutes 18% of an average person's body weight. Indeed, a chubby person's body can be 50% fat without being considered morbidly obese. Adipose tissue may develop almost anywhere areolar tissue is plentiful, but it usually accumulates in subcutaneous tissue, where it also acts as a shock its

tissue proper

(c)

absorber and as insulation. Because fat is a poor conductor of heat, it helps prevent heat loss from the body. Other sites

where

accumulates include surrounding the kidneys, behind the eyeballs, and at genetically determined fat depots such as the abdomen and hips. The adipose tissue just described is sometimes called white fat, or white adipose tissue, to distinguish it from brown fat or brown adipose tissue. Whereas white fat stores nutrients, brown fat confat

nutrient stores to generate heat to warm the body. The richly vascular brown fat occurs only in babies who (as yet) lack the ability to produce body heat by shivering. Most such deposits are located between the shoulder blades, on the antero-

sumes

its

and on the anterior abdominal wall. Whereas the abundant fat beneath the skin

lateral neck,

serves the general nutrient needs of the entire body,

smaller depots of fat serve the local nutrient needs of highly active organs. Such depots occur around the

hard-working heart and around lymph nodes (where cells of the immune system are furiously fighting infection), within some muscles, and as individual fat cells in the bone marrow, where new blood cells are produced at a rapid rate. Many of these local depots offer special lipids that are highly enriched.

Chapter 4

(d)

Tissue:

The

133

Living Fabric

Connective tissue proper: loose connective tissue, reticular

Description: Network of reticular fibers in a ground substance; reticular cells lie on the network.

typical loose

Function: Fibers form a

soft internal skeleton

(stroma) that supports other cell types including white blood cells, mast cells, and

macrophages. White blood (lymphocyte)

Location: Lymphoid organs (lymph nodes, bone marrow, and spleen).

cell

Reticular fibers

Mast

cells

Spleen

Photomicrograph: Dark-staining network

of reticular

connective

tissue fibers forming the internal skeleton of the spleen (350x).

FIGURE

4.8

(continued) Connective tissue proper

(d).

Reticular Connective Tissue Reticular connective tissue resembles areolar connective tissue, but the only fibers in its matrix are reticular fibers,

which form

a delicate

network along which

blasts called reticular cells 4.8d).

Although

lie

fibro-

scattered (Figure

reticular fibers are widely distrib-

uted in the body, reticular tissue

is

limited to certain

forms a labyrinth-like stroma (literally, "bed" or "mattress"), or internal framework, that can support many free blood cells (largely lymphocytes) in lymph nodes, the spleen, and bone marrow. sites.

It

Dense Regular Connective Tissue

Dense

reg-

ular connective tissue (Figure 4.8e) is one variety of the dense connective tissues, all of which have fibers as their

predominant element. For

this reason, the

dense connective tissues are often referred to as fibrous connective tissues. Dense regular connective tissue contains closely packed bundles of collagen fibers running in the same direction, parallel to the direction of pull. This results in white, flexible structures with great resistance to tension (pulling forces) where the tension is exerted in a single direction. Crowded between the collagen fibers are rows of fibroblasts that continuously manufacture the fibers and scant ground substance. As seen in Figure 4.8e, collagen fibers are slightly wavy.

This allows the tissue to stretch a little, but once the out by a pulling force, there is no further "give" to this tissue. Unlike our model (areolar) connective tissue, this tissue has few cells other than fibroblasts and it is poorly vascularized. With its enormous tensile strength, dense regular connective tissue forms the tendons, cords that attach muscles to bones, and flat, sheetlike tendons called aponeuroses (ap"o-nu-ro'sez) that attach muscles to other muscles or to bones. It also forms the ligaments that bind bones together at joints. Ligaments contain more elastic fibers than tendons and are slightly more stretchy. A few ligaments, such as the ligamenta nuchae and flava connecting adjacent vertebrae, are very elastic. Indeed, their content of elastic fibers is so high that the connective tissue in those structures is referred to as elastic connective fibers are straightened

tissue.

Dense Irregular Connective Tissue

Dense

same

structural

irregular connective tissue has the

elements as the regular variety. However, the bundles of collagen fibers are much thicker and they are arranged irregularly; that is, they run in more than one plane (Figure 4.8f). This type of tissue forms sheets in body areas where tension is exerted from many different directions. It is found in the skin as

134

Unit

I

Organization of the Body

Connective tissue proper: dense connective tissue, dense regular

(e)

Description: Primarily parallel collagen fibers: a few elastin fibers; major cell type is the fibroblast.

Collagen fibers

Function: Attaches muscles to bones or to muscles; attaches bones to bones; withstands great tensile stress

applied

in

one

when

pulling force

is

direction.

Location: Tendons, most ligaments, aponeuroses.

Nuclei of fibroblasts

Shoulder joint

Ligament

Photomicrograph: Dense regular connective

tissue from a

tendon (1000x).

Tendon

Connective tissue proper: dense connective tissue, dense irregular

(f)

Description: Primarily irregularly arranged collagen fibers; some elastic fibers; major cell type is the fibroblast. Nuclei of fibroblasts

Function: Able in

many

to withstand tension

exerted

directions; provides structural

strength.

Location: Dermis of the skin; submucosa of digestive tract; fibrous capsules of organs

and

of joints.

Collagen fibers

Fibrous joint

capsule

Photomicrograph: Dense dermis of the skin (400x).

FIGURE

4.8

(continued) Connective tissue proper (e

and

f).

irregular connective tissue from the

Chapter 4

(g) Cartilage:

Tissue:

The

135

Living Fabric

hyaline

Description: Amorphous but firm matrix; collagen fibers form an imperceptible network; chondroblasts produce the matrix and when mature (chondrocytes) lie in lacunae.

Function: Supports and reinforces; has resilient cushioning properties; resists compressive stress.

Location: Forms most of the embryonic skeleton; covers the joint cavities; ribs;

ends

of long

bones

forms costal cartilages

cartilages of the nose, trachea,

in

of the

Chondrocyte

and

in

lacuna

larynx.

Matrix

Costal cartilages

FIGURE

4.8

Photomicrograph: Hyaline

(continued) Cartilage

the leathery dermis, and

(g).

forms fibrous joint capsules and the fibrous coverings that surround some

organs

(testes,

cartilage from the trachea (300x).

it

kidneys, bones, cartilages, muscles,

ing widely separated, so chondrocytes, or mature cartilage cells, are typically found in small groups within cavities called lacunae (lah-ku'ne; "pits").

and nerves).

*tDk HOMEOSTATIC IMBALANCE

Cartilage Cartilage (kar'ti-lij), which stands up to both tension and compression, has qualities intermediate between dense connective tissue and bone. It is tough but flexible, providing a resilient rigidity to the structures it supports. Cartilage lacks nerve fibers and is avascular. It receives its nutrients

by diffusion from

blood vessels located in the connective tissue membrane (perichondrium) surrounding it. Its ground substance contains large amounts of the GAGs chrondroitin sulfate and hyaluronic acid. The ground substance contains firmly bound collagen fibers and in some cases elastic fibers, and is usually quite firm. Cartilage matrix also contains an excep-

amount of tissue fluid; in fact, cartilage is up 80% water! The movement of tissue fluid in its

tional to

matrix enables cartilage to rebound after being compressed and also helps to nourish the cartilage cells. Chondroblasts, the predominant cell type in growing cartilage, produce new matrix until the skeleton stops growing at the end of adolescence. The firm cartilage matrix prevents the cells from becom-

avascular and aging cartilage cells lose their ability to divide, cartilages heal slowly when injured. This phenomenon is excruciatingly familiar to those who have experienced sports injuries. During later life, cartilages tend to calcify or even ossify (become bony). In such cases, the chon-

Because cartilage

is

drocytes are poorly nourished and die.

•

There are three varieties of cartilage: hyaline carand ftbrocartilage, each dominated by a particular fiber type.

tilage, elastic cartilage,

Hyaline Cartilage lin),

or gristle,

is

the

Hyaline cartilage

most abundant

(hi'ah-

cartilage type in

the body. Although it contains large numbers of collagen fibers, they are not apparent and the matrix appears amorphous and glassy [hyalin = glass) blue-

white when viewed by the unaided eye (Figure Chondrocytes account for only 1-10% of the lage volume.

4.8g). carti-

136

Unit

I

Organization of the Body

(h) Cartilage: elastic

Chondrocyte in

lacuna

Elastic fibers

(i)

Cartilage: fibre-cartilage

Description: Matrix similar to but less firm than that in hyaline cartilage; thick collagen fibers predominate.

Function: Tensile strength with the absorb compressive shock.

ability to

Location: Intervertebral discs; pubic symphysis; discs of knee joint. •

Chondrocytes in lacunae

Intervertebral

discs

Collagen fiber

Photomicrograph: disc (200x).

FIGURE

4.8

(continued) Cartilage

(h

and

i).

Fibrocartilage of

an

intervertebral

Chapter 4

(j)

Tissue:

The

Living Fabric

137

Others: bone (osseous tissue)

\'

Description: Hard, calcified matrix containing collagen fibers; osteocytes lie in lacunae. Very well vascularized.

i

many

f aip si e///xeiu auj

p

p

body

is a slight depression, the mandibular symphysis (sim'fih-sis), indicating where the two mandibular bones fused during infancy (see Figure 7.2a). Large mandibular foramina, one on the medial surface of each ramus, permit the nerves responsible for tooth sensation to pass to the teeth in the lower jaw. Dentists inject Novocain into these foramina to prevent pain while working on the lower teeth. The mental foramina, openings on the lateral aspects of the mandibular body, allow blood vessels and nerves to pass to the skin of the chin [ment = chin) and lower lip.

Chapter 7

Maxillary Bones

213

The Skeleton

and the perpendicular plate

The maxillary bones,

or

maxillae

"jaws") (see Figures 7.2 to 7.4

and

(mak-sil'le;

7.8b), are fused

of the ethmoid bone posthey attach to the cartilages that form most of the skeleton of the external nose. teriorly. Inferiorly

They form

the upper jaw and the central portion of the facial skeleton. All facial bones except the mandible articulate with the maxillae. Hence,

The

the maxillae are considered the keystone bones of

bones contribute

the facial skeleton. The maxillae carry the upper teeth in their alveolar margins. Just inferior to the nose the maxillae

(see Figures 7.2a

medially.

meet medially forming the pointed anterior nasal spine at their junction. The palatine (pa'lah-tin) processes of the maxillae project posteriorly from the alveolar margins and fuse medially, forming the anterior two -thirds of the hard palate, or bony roof of

Lacrimal Bones delicate fingernail-shaped lacrimal (lak'ri-mal) to the medial walls of

and

7.3a).

They

each orbit with the

articulate

bone superiorly, the ethmoid bone posteriorly, and the maxillae anteriorly. Each lacrimal bone contains a deep groove that helps form a lacrimal fossa. The lacrimal fossa houses the lacrimal sac, part of the passageway that allows tears to drain from the frontal

eye surface into the nasal cavity [lacrima

=

tears).

Palatine Bones

the mouth (see Figures 7.3b and 7.4a). Just posterior to the teeth is a midline foramen, called the incisive fossa, which serves as a passageway for blood vessels

Each L-shaped palatine bone is fashioned from two bony plates, the horizontal and perpendicular, and has

and nerves.

three important articular processes, the pyramidal,

The

frontal bone,

sphenoidal, and orbital (Figures 7.10a, 7.4a, and 7.8c). The horizontal plates complete the posterior portion

The

dicular (vertical) plates form part of the posterolateral

frontal processes extend superiorly to the

forming part of the lateral aspects of the bridge of the nose (see Figures 7.2a and 7.8b). regions that flank the nasal cavity laterally con-

tain the maxillary sinuses (Figure 7.1 of the paranasal sinuses.

1),

the largest

They extend from

upper teeth. Laterally, the maxillae articuwith the zygomatic bones via their zygomatic

processes.

The inferior orbital fissure is located deep within the orbit (see Figure 7.2a) at the junction of the maxilla with the greater wing of the sphenoid. It permits the zygomatic nerve, the maxillary nerve (a branch of cranial nerve V), and blood vessels to pass to the face. Just below the eye socket on each side is an infraorbital foramen that allows the nerve and artery to reach the face.

hard palate. The superiorly projecting perpen-

walls of the nasal cavity and a small part of the orbits.

the or-

bits to the late

of the

infraorbital

Vomer The

plow-shaped vomer (vo'mer "plow") lies in the nasal cavity, where it forms part of the nasal septum (see Figures 7.2a and 7.10b). It is discussed below in connection with the nasal cavity. slender,

Inferior Nasal

The

;

Conchae

paired inferior nasal conchae are thin, curved

bones in the nasal

cavity.

They project medially from

the lateral walls of the nasal cavity, just inferior to the middle nasal conchae of the ethmoid bone (see

Zygomatic Bones The irregularly shaped zygomatic bones (see Figures 7.2a, 7.3a, and 7.4a) are commonly called the cheekbones [zygoma = cheekbone). They articulate with the zygomatic processes of the temporal bones posteriorly, the zygomatic process of the frontal bone su-

and with the zygomatic processes of the maxillae anteriorly. The zygomatic bones form the prominences of the cheeks and part of the inferolat-

Figures 7.2a and 7.10a).

They

are the largest of the

three pairs of conchae and, like the others, they form part of the lateral walls of the nasal cavity.

Special Characteristics of

the Orbits and Nasal Cavity

periorly,

eral

margins of the

orbits.

thin, basically rectangular nasal (na'zal)

bones

frontal

bone

are

and

7.3a).

They

articulate

superiorly, the maxillary

bones

is

provided here to pull the parts together.

with the

The Orbits The orbits are bony

laterally,

firmly encased and cushioned by fatty

are fused medially, forming the bridge of the nose (see Figures 7.2a

and the nasal formed from an amazing number of bones. Thus, even though the individual bones forming these structures have been described, a brief restricted skull regions, the orbits

cavity,

summary

Nasal Bones

The

Two

cavities in

which the eyes tissue.

are

The

-

214

Unit

II

Covering, Support, and

Movement

of the

Body

-

(a)

Superior

Roof of

orbital fissure

orbit

Supraorbital foramen

Optic canal

Lesser wing ofsphenoid bone Orbital plate of frontal

-

Medial wall

bone Sphenoid body

Orbital plate

Lateral wall of orbit

of

Zygomatic process of frontal bone

-

Frontal process of maxilla

Greater wing of sphenoid bone

-Lacrimal bone

Orbital surface of

Nasal bone

zygomatic bone

Floor of orbit

Inferior orbital fissure

Infraorbital

ethmoid bone

-Orbital

groove

process of

palatine

Zygomatic bone

bone

-Orbital surface of

maxillary Infraorbital

(b)

FIGURE

7.9

bone

Zygomatic bone

foramen

Special anatomical characteristics of the orbits. The contribution bones forming the right orbit is illustrated, (a) Photograph,

of each of the seven (b)

Diagrammatic view. (See

A

Brief Atlas of the

Human

Body, Figure

muscles that move the eyes and the tear-producing lacrimal glands are also housed in the orbits. The walls of each orbit are formed by parts of seven bones the frontal, sphenoid, zygomatic, maxilla,

—

14.)

palatine, lacrimal,

tionships are

and ethmoid bones. Their

shown

in Figure 7.9. Also seen in the

orbits are the superior

and the optic

rela-

and

inferior orbital fissures

canals, described earlier.

Chapter 7

The Skeleton

215

Frontal sinus

Superior, middle, inferior

Superior nasal concha

and

- Ethmoid bone

meatus Middle nasal concha Inferior nasal

concha

Nasal bone

Anterior nasal spine

Maxillary bone (palatine process)

i—

Sphenoid sinus

Sphenoid bone— Pterygoid process

Palatine bone (perpendicular

Palatine

bone

(horizontal plate)

plate)

(a)

Crista

Ethmoid bone

—

galli

Cribriform

Frontal sinus

_ plate

Sella turcica

Nasal bone

Sphenoid sinus

Perpendicular plate of

ethmoid bone

Septal cartilage

Vomer Palatine

bone

Alveolar margin of maxilla

Palatine process of maxilla

(b)

FIGURE 7.10

Special anatomical characteristics of the nasal cavity. Bones forming the left lateral wall of the nasal cavity, (b) The contribution of the ethmoid, vomer, and cartilage to the nasal septum. (See A Brief Atlas of the Human (a)

Body, Figure

1

5.)

The Nasal Cavity The nasal cavity is constructed of bone and hyaline cartilage (Figure 7.10a). The roof of the nasal cavity is formed by the cribriform plate of the ethmoid. The lateral walls are largely

shaped by the superior and

middle conchae of the ethmoid bone, the perpendicular plates of the palatine bones, and the inferior nasal conchae. The depressions under cover of the

conchae on the lateral walls are called meatuses [meatus = passage), so there are superior, middle,

216

Unit

II

Covering, Support, and

Movement

of the

Body

Greater horn

Lesser horn

Body

FIGURE 7.12 Anatomical location and structure of the hyoid bone. The hyoid bone is suspended in the midanterior neck by ligaments attached to the lesser horns (cornua) and the styloid processes of the temporal bones.

Paranasal Sinuses Five skull bones

— the

ethmoid, and paired maxillary bones contain mucosa-lined, air-filled sinuses that cause them to look rather moth-eaten in an X-ray image. These particular sinuses are called paranasal sinuses because they cluster around the nasal cavity (Figure 7.11). Small openings connect the sinuses to the nasal cavity and

FIGURE (b)

7.11

Paranasal sinuses,

(a)

Anterior aspect,

Medial aspect.

act as

"two-way

frontal, sphenoid,

—

streets"; air enters the sinuses

from

mucus formed by the sinus muthe nasal cavity. The mucosae of

the nasal cavity, and

cosae drains into the sinuses also help to warm and humidify inspired air. The paranasal sinuses lighten the skull and enhance the resonance of the voice.

and inferior meatuses. The floor of the nasal cavity is formed by the palatine processes of the maxillae and the palatine bones. The nasal cavity is divided into right and left parts by the nasal septum. The bony portion of the septum is formed by the vomer inferiorly and the perpendicular plate of the ethmoid bone superiorly (Figure 7.10b). A sheet of cartilage called the septal cartilage completes the septum anteriorly.

The

septum and conchae are covered with a mucus-secreting mucosa that moistens and warms the entering air and helps cleanse it of debris. The nasal

scroll-shaped conchae increase the turbulence of air flowing through the nasal cavity. This swirling forces more of the inhaled air into contact with the warm, damp mucosa and encourages trapping of airborne particles (dust, pollen, bacteria) in the sticky mucus.

The Hyoid Bone Though not (hi'oid;

really part of the

skull,

"U-shaped") bone (Figure 7.12)

the hyoid

lies just infe-

mandible in the anterior neck. The hyoid bone is unique in that it is the only bone of the body that does not articulate directly with any other bone. Instead, it is anchored by the narrow stylohyoid ligaments to the styloid processes of the temporal bones. Horseshoe-shaped, with a body and two pairs of horns, or cornua, the hyoid bone acts as a movable base for the tongue. Its body and greater horns are attachment points for neck muscles that raise and lower the larynx during swallowing and speech. rior to the

*

*

*

Table 7.1 summarizes the bones of the skull.

TABLE

7

i 1

Diarthrntir* uniaxia

f

'

pxion

extension of forearm

Radius and ulna

Synovial; pivot

(proximal^

Diarthrotic; uniaxial; rotation of idOlUb diOUilO lUily dXlb Ol forearm to allow pronation and

supination ndUlUull

\ct

i

rxdUlUb

duO

ulild

(distal)

Wrist

Radius and proximal

(radiocarpal)

carpals

Intercarpal

Adjacent carpals

Oarnnmpta carnal

fam^l

of digit

metacarpal

1

oynuvidi, pivoL \con-

L-'Idl

tains articular disc)

(convex head of ulna rotates ulnar notch of radius)

Synovial; condyloid

ftr^np7iijml

Synovial; plane

3nH

Svnnvia

*

^^nn p

Diarthrotic; biaxial; flexion,

Diarthrotic; gliding P)i 3 rt h rot f' l_y lOILIIIL-'Ll'— i

,

and

oi^yi^ UluAIOI,

f ICAIUI pyinnIj 1

extension, abduction, adduction, circumduction, opposition of metacarpal 1

1

Carpometacarpal of digits 2-5

Carpal(s)

Knuckle (metacarpo-

Metacarpal and proximal phalanx

Synovial; condyloid

Adjacent phalanges

Synovial; hinge

Synovial; plane

metacarpal(s)

Diarthrotic; gliding of

metacarpals Diarthrotic; biaxial; flexion,

extension, abduction, adduction, circumduction of fingers

phalangeal)

(interphalangeal)

in

extension, abduction, adduction, circumduction of hand

(thumb)

Finger

ImULIC, UllldXIdl, lUldllUN

Diarthrotic; uniaxial; flexion,

extension of fingers

Chapter 8

TABLE

8

>2

259

Joints

(continued) Functional Type;

Articulating Illustration

Joint

Bones

Structural Type*

Sacroiliac

Sacrum and coxal bone

Synovial; plane

Movements A/lowed Diarthrotic;

little

movement,

slight gliding possible

(more during pregnancy) Pubic symphysis

Pubic bones

Amphiarthrotic; slight

Cartilaginous;

movement (enhanced

symphysis

during

pregnancy) Hip bone and femur

Hip (coxal)

Synovial; ball

and

socket

Femur and

Knee

tibia

(tibiofemoral)

Femur and

Knee

patella

Diarthrotic; multiaxial; flexion,

extension, abduction, adduction, rotation, circumduction of thigh

Synovial; modified

Diarthrotic; biaxial; flexion,

hinge r (contains articular discs)

extension of leg, allowed

Synovial; plane

Diarthrotic; gliding of patella

Synovial; plane

Diarthrotic; gliding of fibula

some

rotation

(femoropatellar) Tibiofibular

Tibia

and

fibula

(proximally) Tibiofibular

Tibia

and

fibula (distally)

Fibrous; syndesmosis

Synarthrotic; slight "give"

during dorsiflexion Ankle

Tibia

and

fibula with talus

Synovial; hinge

Diarthrotic; uniaxial;

dorsiflexion,

and plantar

flexion

of foot

Adjacent tarsals

Intertarsal

Synovial; plane

Diarthrotic; gliding; inversion

and eversion of foot Tarsometatarsal

Tarsal(s)

and metatarsal(s)

Synovial; plane

Diarthrotic; gliding of

metatarsals Metatarsophalangeal

Metatarsal and proximal phalanx

Synovial; condyloid

Toe

Adjacent phalanges

Synovial; hinge

(interpha-

^hese modified hinge

circles;

cartilaginous joints by blue circles; synovial joints by purple circles,

joints are structurally bicondylar.

about 6% of its length before it snaps. Thus, when ligaments are the major means of bracing a joint, the joint is not very stable.

Muscle Tone most

muscle tendons that cross the joint are the most important stabilizing factor. These tendons are kept taut at all times by the tone of their muscles. (Muscle tone is defined as low levels of contractile activity in relaxed muscles that keep the muscles healthy and ready to react to stimulation.) Muscle tone is extremely important in reinforcing the shoulder and knee joints and the For

Diarthrotic; uniaxial; flexion;

extension of toes

langeal)

'Fibrous joints indicated by orange

Diarthrotic; biaxial; flexion,

extension, abduction, adduction, circumduction of great toe

joints, the

arches of the foot.

Movements Allowed by Synovial Joints Every skeletal muscle of the body is attached to bone or other connective tissue structures at no fewer than two points. The muscle's origin is attached to the immovable (or less movable) bone. Its other end, the insertion, is attached to the movable bone. Body movement occurs when muscles contract across joints and their insertion moves toward their origin. The movements can be described in directional terms relative to the lines, or axes, around which the body part moves and the planes of space along which the movement occurs, that is, along the transverse, frontal, or sagittal plane. (These planes

were described in Chapter

1.)

260

Unit

II

Covering, Support, and

Movement

of the

Body"

Range of motion allowed by synovial joints from nonaxial movement (slipping movements only since there is no axis around which movement can occur) to uniaxial movement (movement in one plane) to biaxial movement (movement in two planes) to multiaxial movement (movement in or around all three planes of space and axes). Range of motion varies greatly in different people. In some, such as trained gymnasts or acrobats, range of

varies

joint

movement may be

extraordinary.

The

ranges of

motion at the major joints are given in Table 8.2. There are three general types of movements: gliding, angular movements, and rotation. The most common body movements allowed by synovial joints are described next and illustrated in Figure 8.5.

Gliding

FIGURE

Movements

(a)

Gliding movements (Figure

FIGURE

flat,

8.5 (continued)

movements.

synovial joints.

known as movements. One

bone surface glides or slips over another (back-and-forth and side-to-side) without appreciable angulation or rotation. Gliding movements occur at the intercarpal and intertarsal joints, and between the flat articular processes of the vertebrae, as well as in combination with other movements (see Table 8.2). or nearly

Movement allowed by

Gliding movements.

8.5a), also

translation, are the simplest joint flat,

8.5

Movement allowed by

Angular Movements Angular movements (Figure 8.5b— f)

increase or

decrease the angle between two bones. These movements may occur in any plane of the body and include flexion, extension, hyperextension, abduction, adduction, and circumduction.

synovial joints,

(b)

Angular

Chapter 8

Hyperextension

FIGURE

8.5 (continued)

261

Joints

Extension

Movements allowed by

synovial joints, (c-e) Angular movements.

Flexion Flexion (flek'shun) is a bending movement, usually along the sagittal plane, that decreases the angle of the joint and brings the articulating bones closer together. Examples include bending the head forward on the chest (Figure 8.5d) and bending the body trunk or the knee from a straight to an angled position (Figure 8.5b and c). As a less obvious example, the arm is flexed at the shoulder when the arm is lifted in an anterior direction (Figure 8.5b).

Extension occurs at the

Extension

same

is

the reverse of flexion and

movement

along the sagittal plane that increases the angle between the articulating bones, such as straightening a flexed neck, body trunk, elbow, or knee (Figure 8.5b-d). Bending the head backward beyond its straight (upright) position is called hyperextension. At the shoulder, extension carries the arm to a point posterior to the shoulder joint. joints. It involves

proaches the shin

is

dorsiflexion (corresponds to

wrist extension), whereas depressing the foot (point-

ing the toes)

is

plantar flexion (corresponds to wrist

flexion).

Abduction Abduction ("moving away") is movement of a limb away from the midline or median plane of the body, along the frontal plane. Raising the arm (Figure 8.5f) or thigh laterally is an example

of abduction.

When

the term

is

used to

in-

movement of the fingers or toes, it means spreading them apart. In this case "midline" is the longest digit: the third finger or second toe. Notice, however, that lateral bending of the trunk away from the body midline in the frontal plane is called lateral flexion, not abduction. dicate the

Adduction

Adduction ("moving toward")

is

movement

the

Dorsiflexion

and Plantar Flexion of the Foot The up-and-down movements of the foot at the ankle joint are given more specific names (Figure 8.5e).

of a opposite of abduction, so limb toward the body midline or, in the case of the digits, toward the midline of the hand or foot (Figure

Lifting the foot so that its superior surface ap-

8.5f).

it

is

the

262

Unit

II

Covering, Support, and

Movement

of the

Circumduction Circumduction (Figure 8.5f) is moving a limb so that it describes a cone in space [circum = around; duco = to draw). The distal end of the limb moves in a circle, while the point of the cone (the shoulder or hip joint) is more or less stationary. A pitcher winding up to throw a circumducting his or her pitching arm. Because circumduction consists of flexion, abduction, extension, and adduction performed in

ball is actually

succession,

it is

many muscles

the quickest way to exercise the move the hip and shoulder

that

ball-and-socket joints.

Rotation Rotation

is

the turning of a bone around

its

own

long axis. It is the only movement allowed between the first two cervical vertebrae and is common at the hip (Figure 8.5g) and shoulder joints. Rotation may be directed toward the midline or away from it. For example, in medial rotation of the thigh, the femur's anterior surface moves toward the median plane of the body; lateral rotation is the opposite

movement.

Body

Special Certain

Movements movements do not

categories

and occur

these special

fit

into any of the above

at only a

movements

few

joints.

Some

of

are "illustrated in Figure 8.6.

Supination and Pronation The terms supination (soo"pi-na'shun; "turning backward") and pronation (pro-na'shun; "turning forward") refer to the movements of the radius around the ulna (Figure 8.6a). Rotating the forearm laterally so that the palm faces anteriorly or superiorly is supination. In the anatomical position, the hand is supinated and the radius and ulna are parallel. In pronation, the forearm rotates medially and the palm faces posteriorly or inferiorly. Pronation moves the distal end of the radius across the ulna so that the two bones form an X. This is the forearm's position when we are standing in a relaxed

manner. Pronation is a much weaker movement than supination. Tricks to help you keep these terms straight: If you lifted a cup of soup up to your mouth on your palm, you would be supinating ("soup"-inating), and a pro basketball player pronates his or her forearm to dribble the ball.

Chapter 8 Which hand position

—

Joints

263

pronation or supination-

characteristic of the anatomical position?

Supination (radius

and ulna

are parallel)

(a)

(b)

(d)

Elevation and depression

(e)

Opposition

Supination (S) and pronation (P)

Inversion and eversion

Inversion and Eversion

Inversion and ever-

sion are special movements of the foot (Figure 8.6b). In inversion, the sole of the foot turns medially. In eversion, the sole faces laterally.

Protraction and Retraction

Nonangular ante-

and posterior movements in a transverse plane and retraction, respectively (Figure 8.6c). The mandible is protracted when you jut out your jaw and retracted when you move it back to its original position. rior

are called protraction

Elevation means Elevation and Depression body part superiorly (Figure 8.6d). For example, the scapulae are elevated when you shrug your lifting a

(c)

FIGURE 8.6 Special body movements, (a) Supination and pronation, (b) Inversion and eversion. (c) Protraction and retraction, (d) Elevation and depression, (e)

Opposition.

I

uoneuidnc;

Moving

the elevated part inferiorly is depression. During chewing, the mandible is alternately elevated and depressed. shoulders.

Protraction and retraction

The saddle joint between metacarpal Opposition 1 and the carpals allows a movement called opposition of the thumb (Figure 8.6e). This movement is the action taken when you touch your thumb to the

264

Unit

II

Covering, Support, and

Movement

of the

Body

Plane joint

^pTranslational

lUI Uniaxial (^Biaxial Qlvlultiaxial

FIGURE

Types of synovial

8.7

joints.

Dashed

lines

indicate the articulating bones, (a) Plane joint (e.g.,

and intertarsal joints), (b) Hinge and interphalangeal joints).

intercarpal joints

joint (e.g.,

elbow Hinge

on the same hand. It is opposition that makes the human hand such a fine tool for grasping and manipulating objects. tips of the other fingers

Plane Joints In plane joints (Figure 8.7a) the articular surfaces are essentially flat, and they allow only short gliding or translational tertarsal joints,

in

all

synovial joints have structural features

common, they do not have

plan. Based

which

on the shape

a

common

structural

of their articular surfaces,

in turn determine the

movements

allowed,

synovial joints can be classified further into six jor categories dle,

— plane,

ma-

hinge, pivot, condyloid, sad-

and ball-and-socket

joints.

movements. Examples

ing joints introduced earlier

Types of Synovial Joints Although

joint

and the

are the glid-

— the intercarpal and

joints

ticular processes. Gliding does

around any axis, and gliding amples of nonaxial joints.

in-

between vertebral arnot involve rotation

joints are the only ex-

Chapter 8

Joints

265

Pivot joint

(e) Saddle joint

(d) Condyloid joint

FIGURE (c)

8.7 (continued)

Types of synovial

joints.

Condyloid Saddle joint

Pivot joint (e.g., proximal radioulnar joint), (d)

metacarpophalangeal joints), (e) carpometacarpal joint of the thumb), (f) Ball-and-

joint (e.g., (e.g.,

socket joint (shoulder

f) Ball-and-socket joint

joint).

Hinge Joints

you

In hinge joints (Figure 8.7b), a cylindrical projection

"no." Another

of

one bone

fits

into a trough- shaped surface

on an-

to

move your head from

where the head

is

side to side to indicate

the proximal radioulnar joint,

of the radius rotates within a ringlike

other.

Motion is along a single plane and resembles that of a mechanical hinge. The uniaxial hinge

ligament secured to the ulna.

joints

permit flexion and extension only, typified by bending and straightening the elbow and interpha-

Condyloid Joints

langeal joints.

In condyloid joints (kon'di-loid; "knuckle-like"), or ellipsoidal joints, the oval articular surface of one bone fits into a complementary depression in

Pivot Joints In a pivot joint (Figure 8.7c), the rounded end of one bone protrudes into a "sleeve" or ring composed of bone (and possibly ligaments) of another. The only movement allowed is uniaxial rotation of one bone around its own long axis. An example is the joint between the atlas and dens of the axis, which allows

another (Figure 8.7d). The important characteristic is that both articulating surfaces are oval. The biaxial condyloid joints permit all angular motions, that is, flexion and extension, abduction and adduction, and circumduction. The radiocarpal (wrist) joints and the metacarpophalangeal (knuckle) joints are typical condyloid joints.

266

Unit

II

Covering, Support, and

Movement

of the

Body

The knee

Saddle Joints Saddle joints (Figure 8.7e) resemble condyloid but they allow greater freedom of movement. Each articular surface has both concave and convex areas; that is, it is shaped like a saddle. The articular surfaces then fit together, concave to convex surfaces. The most clear-cut examples of saddle joints in the body are the carpometacarpal joints of the thumbs, and the movements allowed by these joints are clearly demonstrated by twiddling your thumbs. joints,

joint is

unique in that

its joint

cavity

is

only partially enclosed by a capsule. The relatively thin articular capsule is present only on the sides and posterior aspects of the knee, where it covers the bulk of the femoral and tibial condyles. Anteriorly, where the capsule is absent, three broad ligaments

run from the patella to the tibia below. These are the patellar ligament flanked by the medial and lateral patellar retinacula

(ret"i-nak'u-lah

;

"retainers"),

which merge imperceptibly into the articular capsule on each side (Figure 8.8c). The patellar ligament and retinacula are actually continuations of the tendon

In ball-and-socket joints (Figure 8.7f), the spherical

bone articulates with the cuplike socket of another. These joints are multiaxial and the most freely moving synovial joints. or hemispherical head of one

Universal

movement

is

and planes, including

muscle of the anterior thigh. Physicians tap the patellar ligament to test the knee-

of the bulky quadriceps

Ball-and-Socket Joints

allowed (that

is,

in

all

axes

The shoulder and

rotation).

hip joints are examples.

jerk reflex.

The

synovial cavity of the knee joint has a complicated shape, with several extensions that lead into "blind alleys." At least a dozen bursae are associated

with this

Selected Synovial Joints we examine four and elbow) in detail. All

In this section,

joints (knee, shoul-

der, hip,

of these joints

have

the five distinguishing characteristics of synovial joints, and we will not discuss these common features again. Instead, we will emphasize the unique structural features, functional abilities, and, in certain cases, functional weaknesses of each of these joints.

Knee Joint in the

joint

is

the largest and

body (Figure

8.8). It

most complex

joint

allows extension, flexion,

and some rotation. Despite its single joint cavity, the knee consists of three joints in one: an intermediate one between the patella and the lower end of the femur (the femoropatellar joint), and lateral and medial joints (collectively

known

as the tibiofemoral

between the femoral condyles above and the C-shaped menisci, or semilunar cartilages, of the tibia below. Besides deepening the shallow tibial arjoint)

menisci help prevent side-to-side rocking of the femur on the tibia and absorb shock transmitted to the knee joint. However, the menisci are attached only at their outer margins and are frequently torn free. The tibiofemoral joint acts primarily as a hinge, permitting flexion and extension. However, structurally it is a bicondylar joint. Some rotation is possible when the knee is partly flexed, but when it is extended, side-to-side movements and rotation are strongly resisted by ligaments and the menisci. The femoropatellar joint is a plane joint, and the patella glides across the distal end of the femur during knee movements. ticular surfaces, the

example,

prepatellar bursa,

knee

The knee

some

joint,

For

8.8a.

is

shown in Figure the subcutaneous often injured when the

which

of

are

notice

which

is

bumped.

All three types of joint ligaments stabilize and strengthen the capsule of the knee joint. The capsular and extracapsular ligaments all act to prevent hyperextension of the knee and are stretched taut when the knee is extended. These include the

1

following:

The

extracapsular fibular and tibial collateral ligaments are also critical in preventing lateral or 1.

medial rotation when the knee is extended. The broad flat tibial collateral ligament runs from the medial epicondyle of the femur to the medial condyle of the tibial shaft below and is fused to the medial meniscus. 2.

The oblique

popliteal ligament (pop'li-te'al)

j

j

j

is ac-

tendon of the semimembranosus muscle that fuses with the capsule and strengthens the posterior aspect of the knee joint (Figure 8.8e). tually part of the

3.

The arcuate

from the head

popliteal ligament arcs superiorly

of the fibula

and reinforces the

joint

capsule posteriorly.

The

knee's intracapsular ligaments are called cruciate ligaments (kroo'she-at) because they cross each other, forming an X [cruci = cross) in the notch between the femoral condyles. They help prevent anterior-posterior displacement of the articular sur-

and secure the articulating bones when we stand (see Figure 8.8b). Although these ligaments are in the joint capsule, they are outside the synovial

faces

and synovial membrane nearly covers their surfaces. Note that the two cruciate ligaments both run up to the femur and are named for their tibial attachment site. The anterior cruciate ligament at-

I I

cavity,

I

I j

taches to the anterior intercondylar area of the

From ward

there

it

tibia. 1

passes posteriorly, laterally, and up- J femur on the medial side of its!

to attach to the

Chapter 8 Tendon

267

Joints

of

Posterior

quadriceps femoris

cruciate

ligament Fibular

Medial condyle

collateral

ligament

Suprapatellar

bursa

Tibial

collateral

Patella

condyle

Subcutaneous

of

prepatellar bursa

femur Anterior cruciate

Synovial cavity Lateral

ligament

Lateral

Lateral

ligament

meniscus

meniscus

Medial Infrapatellar fat

meniscus

pad

semilunar

Tibia

cartilage)

Deep

infrapatellar

bursa Patellar

Patellar ligament

ligament Patella

Fibula

Quadriceps tendon

t

(b)

Tendon

Femur

of

adductor

magnus Articular

Medial head of

capsule

gastrocnemius muscle

Oblique

Medial

popliteal

patellar

ligament

retinaculum Lateral Tibial

head

collateral

gastrocnemius muscle

ligament

of

Patellar

Fibular

ligament

collateral

ligament •Tibia

Arcuate popliteal

Tendon of semimembranosus

ligament

muscle -Tibia

Femoral condyle

(e)

Anterior

FIGURE

cruciate

Midsagittal section, (b) Anterior view of slightly flexed knee

ligament

joint

8.8

Right knee joint relationships,

(a)

tibial

showing the cruciate ligaments. Articular capsule has been removed; the quadriceps tendon is cut and reflected distally. (c) Anterior view, (d) Photograph of an opened knee

condyle

joint

Medial

of the ligaments clothing the knee joint.

Medial

meniscus

corresponds to view

in (b). (e)

Posterior superficial view

268

Unit

lateral condyle.

II

Covering, Support, and

Movement

This ligament prevents forward

of the

Body

slid-

on the femur and checks hyperextension of the knee. It is somewhat lax when the knee is flexed and taut when the knee is extended. The ing of the tibia

stronger posterior cruciate ligament is attached to the posterior intercondylar area of the tibia and passes anteriorly medially and upward to attach to the lateral side of the medial femoral condyle. This ligament prevents backward displacement of the tibia or forward sliding of the femur. The knee capsule is heavily reinforced by muscle tendons. Most important are the strong tendons of the quadriceps muscles of the anterior thigh and the tendon of the semimembranosus muscle posteriorly. Since the muscles associated with the joint are the

main knee

stabilizers, the greater their strength

tone, the less the chance of

The knees have

knee

and

injury.

a built-in locking device that

provides steady support for the body in the standing position. As we begin to stand up, the wheelshaped femoral condyles roll like ball bearings across the flat condyles of the tibia and the flexed leg begins to extend at the knee. Because the lateral femoral condyle stops rolling before the medial condyle stops, the femur spins (rotates) medially on the tibia, until all major ligaments of the knee are twisted and taut and the menisci are compressed. The tension in the ligaments effectively locks the joint into a rigid structure that cannot be flexed again until it is unlocked. This unlocking is accomplished by the popliteus muscle (see Table 10.15, p. 376), which rotates the femur laterally on the tibia, causing the ligaments to become untwisted and slack.

FIGURE 8.9 A common knee injury. Anterior view of a knee being hit by a hockey puck. By separating the femur from the tibia medially, such blows to the lateral side tear both the tibial collateral ligament and the medial meniscus because the two are attached. The anterior cruciate ligament also tears.

ous and competitive. Most ACL injuries occur when a runner changes direction quickly, twisting a hyperextended knee. A torn ACL heals poorly, so repair usually requires a ligament graft using connective tissue taken from one of the larger ligaments (e.g., patellar, Achilles, or

HOMEOSTATIC IMBALANCE Of

semitendinosus).

•

Shoulder (Glenohumeral) Joint

knees are most susceptible to sports injuries because of their high reliance on

In the shoulder joint, stability has been sacrificed to provide the most freely moving joint of the body. The

nonarticular factors for stability and the fact that they carry the body's weight. The knee can absorb a

shoulder joint is a ball-and-socket joint. The large hemispherical head of the humerus fits in the small, shallow glenoid cavity of the scapula (Figure 8.10),

all

body

joints, the

nearly seven times body weight. However, it is very vulnerable to horizontal blows, such as those that occur during blocking and tackling in football. When thinking of common knee injuries, remember the 3 C's: collateral ligaments, vertical

force equal to

cruciate ligaments,

and

cartilages (menisci).

Most

dangerous are lateral blows to the extended knee. These forces tear the tibial collateral ligament and the medial meniscus attached to it, as well as the anterior cruciate ligament (Figure 8.9). It is estimated that 50% of all professional football players have serious knee injuries during their careers. Although less devastating than the injury just described, injuries that affect only the anterior cruciate ligament (ACL) are becoming more common, particularly as

women's

sports

become more

vigor-

on a tee. Although the glenoid deepened by a rim of fibrocartilage,

like a golf ball sitting

cavity

is

slightly

labrum [labrum = lip), it is only about one-third the size of the humeral head and conthe glenoid

tributes little to joint stability.

The articular capsule enclosing the joint cavity (from the margin of the glenoid cavity to the anatomical neck of the humerus) is remarkably thin and loose, qualities that contribute to this joint's freedom of movement. The few ligaments reinforcing the shoulder joint are located primarily on its anterior aspect. The superiorly located coracohumeral ligament (kor'ah-ko-hu'mer-ul) provides the only strong thickening of the capsule and helps support the weight of the upper limb. Three gleno-

— Chapter 8

269

Joints

Acromion

Acromion Coracoid process

Coracoacromial ligament

Coracoid process

Subacromial bursa

Articular

capsule

Coracohumeral Articular

ligament

Glenoid cavity

capsule Greater

reinforced by

tubercle

glenohumeral

humerus

of

Tendon of long head of biceps

Subscapular bursa

Transverse humeral ligament

Tendon

Tendon sheath Tendon of long head of

Glenoid labrum

ligaments

brachii

muscle

Glenohumeral

of the

subscapularis

ligaments

muscle

Tendon

of the subscapularis

Scapula

muscle

biceps

Scapula

brachii

muscle

Posterior

Anterior

(b)

(a)

Acromion cut)

Glenoid

Head of humerus

cavity of

scapula

Capsule Muscle

FIGURE 8.10

joint

relationships,

of

rotator

of

shoulder

(opened)

cuff (cut)

illustrating

Right shoulder joint (a)

some

Anterior superficial view

of the reinforcing ligaments,

associated muscles, and bursae. (b) The shoulder joint, cut

open and viewed from the lateral humerus has been removed,

aspect; the (c) (c)

interior of the

shoulder

joint, anterior view.

humeral ligaments (gle"no-hu'mer-ul) strengthen the front of the capsule somewhat but are weak and

may even be

absent.

Muscle tendons that cross the shoulder joint contribute most to this joint's stability. The "superstabilizer" is the tendon of the long head of the biceps brachii muscle of the arm (Figure 8.10a). This tendon attaches to the superior margin of the glenoid labrum, travels through the joint cavity, and then runs within the intertubercular groove of the

Photograph of the

humerus.

It

secures the head of the

humerus

against the glenoid cavity. Four other tendons (and the associated muscles) make up the rotator cuff.

This cuff encircles the shoulder joint and blends with the articular capsule. The muscles include the subscapularis, supraspinatus, infraspinatus, and teres minor. (The rotator cuff muscles are illus-

trated in Figure 10.14, p. 356.) The rotator cuff can be severely stretched when the arm is vigorously circumducted; this is a common injury of baseball pitchers. As noted in Chapter 7, shoulder dislocations are fairly common. Because the shoulder's

reinforcements are weakest anteriorly and inferiorly, the humerus tends to dislocate in the forward

and downward

direction.

Hip (Coxal) Joint

The

hip joint, like the shoulder joint, is a ball-andsocket joint. It has a good range of motion, but not nearly as wide as the shoulder's range. Movements occur in all possible planes but are limited by the joint's strong ligaments and its deep socket. The hip joint is formed by the articulation of the spherical

270

Unit

II

Movement

Covering, Support, and

Coxal

(hip)

of the

Body

bone

Articular cartilage

Ligament

Acetabular labrum

head of the femur igamentum teres)

Acetabular labrum

of the

Synovial

membrane

Femur

Ligament head of the femur (ligamentum of the

teres)

Head of

femur

Articular

capsule

(cut)

Synovial cavity Articular capsule (b)

(a)

Iliofemoral

Iliofemoral

ligament

ligament Anterior inferior iliac

Ischiofemoral

spine

Pubofemoral

igament

ligament

Greater Greater

trochanter

trochanter of

femur

(c)

FIGURE joint, (b)

8.1 1 Right hip joint relationships, (a) Frontal section through the hip Photograph of the joint interior lateral view, (c) Anterior superficial view,

(d) Posterior superficial view.

head of the femur with the deeply cupped acetaof the hip bone (Figure 8.11). The depth of the acetabulum is enhanced by a circular rim of fi-

bulum

brocartilage called

labrum

the acetabular

(as"e-

and b). The labrum's diamthan that of the head of the femur, and these articular surfaces fit snugly together, so hip tab'u-lar)

eter

(Figure 8.1 la

is less

joint dislocations are rare.

The of the

thick articular capsule extends from the rim

acetabulum to the neck

of the

femur and com-

pletely encloses the joint. Several strong ligaments

reinforce the capsule of the hip joint.

These include

the iliofemoral ligament (il"e-o-fem'o-ral), a strong V-shaped ligament anteriorly; the pubofemoral liga-

ment

(pu"bo-fem'o-ral), a triangular thickening of the

inferior part of the capsule;

and the ischiofemoral

ligament (is"ke-o-fem'o-ral), a spiraling posteriorly located ligament. These ligaments are arranged in such a way that they "screw" the femur head into the acetabulum when a person stands up straight, thereby providing

more

stability.

The ligament

of the head of the femur, also

called the ligamentum teres, is a flat intracapsular band that runs from the femur head to the lower lip of the acetabulum. This ligament is slack during most hip movements, so it is not important in stabi-

mechanical function (if does contain an artery that helps supply the head of the femur. Damage to this artery may lead to severe arthritis of the hip joint. Muscle tendons that cross the joint and the bulky hip and thigh muscles that surround it conlizing the joint. In fact, its

any)

is

unclear, but

it

Chapter 8

271

Joints

Articular

capsule Synovial

membrane Humerus

Humerus

Synovial cavity

Annular igament

Articular cartilage

Fat

pad Coronoid process

Tendon

Lateral

—

epicondyle

of

triceps

Articular

muscle

capsule Bursa Radial collateral

Trochlea

ligament Articular cartilage

>

notch

Olecranon process

(a)

(b)

of the trochlear

Ulna

Humerus Annular ligament

Articular

capsule

Annular Medial epicondyle

Articular

Humerus

ligament

capsule

Ulnar (medial)

Radius

Medial epicondyle

collateral

ligament

Ulnar

Coronoid process

collateral

ligament

Ulna

Ulna (c)

FIGURE 8.12

Right elbow joint relationships, (a) Midsagittal section of Photograph of elbow joint showing the important reinforcing ligaments, medial view, (d) Medial view.

elbow

joint, (b) Lateral view, (c)

and strength. However, the deep socket that securely encloses the femoral head and the strong ligaments contribute most to the statribute to its stability

bility of

the hip joint.

Elbow Joint Our upper limbs

are flexible extensions that permit

us to reach out and manipulate things in our environment. Besides the shoulder joint, the most prominent of the upper limb joints is the elbow. The elbow joint provides a stable and smoothly operating hinge that allows flexion and extension only (Figure 8.12). Within the joint, both the radius and ulna articulate with the condyles of the humerus, but it is the close gripping of the trochlea by the

ulna's trochlear notch that stabilizes this joint.

forms the "hinge" and

A relatively lax articular capsule

extends inferiorly from the humerus to the ulna and to the annular ligament (an'u-lar) surrounding the

head of the radius. Anteriorly and posteriorly, the articular capsule is thin and allows substantial freedom for elbow flexion and extension. However, side-to-side movements are restricted by two strong capsular ligaments: the ulnar collateral ligament medially and the radial collateral ligament, a triangular ligament on the lateral side. Additionally, tendons of several

arm muscles, such

as the biceps

and

triceps, cross

the elbow joint and provide security. The radius is a passive "onlooker" in the angular

head rotates within the annular ligament during supination and pronaelbow movements. However, tion of the forearm.

its

272

Unit

II

Covering, Support, and

Movement

of the

Body

Homeostatic Imbalances of Joints Few

of us pay attention to our joints unless something goes wrong with them. Joint pain and malfunction can be caused by a number of factors, but

most joint problems result from injuries and inflammatory or degenerative conditions.

Common For

Joint Injuries

most of us, sprains and

dislocations are the

common trauma- induced joint injuries,

most

but cartilage

injuries are equally threatening to athletes.

Sprains In a sprain, the ligaments reinforcing a joint are

stretched or torn.

The lumbar

the ankle, and the knee are

region of the spine,

common

sprain

sites.

FIGURE 8.13 Arthroscopic photograph of a torn medial meniscus (Courtesy of the author's tennis game).

Partially torn ligaments will repair themselves, but

they heal slowly because ligaments are so poorly vascularized. Sprains tend to be painful and immobilizing. Completely ruptured ligaments require prompt surgical repair because inflammation in the joint will break down the neighboring tissues and turn the injured ligament to "mush." Surgical repair can be difficult: A ligament consists of hundreds of fibrous strands, and sewing one back together has been compared to trying to sew two hairbrushes together.

When

important ligaments are too severely damaged to be repaired, they must be removed and replaced with grafts or substitute ligaments. For example, a piece of tendon from a muscle, or woven collagen bands, can be stapled to the articulating bones. Alternatively, carbon fibers are implanted in the torn ligament to form a supporting mesh, which is then invaded by fibroblasts that reconstruct the ligament.

arthroscope, a small instrument bearing a and fiber-optic light source, enables the

surgeon to view the joint interior (Figure 8.13), reremove cartilage fragments through one or more tiny slits, minimizing tissue damage and scarring. Removal of part of a meniscus does not severely impair knee joint mobility, but the joint is definitely less stable.

pair a ligament, or

Dislocations

A

dislocation (luxation) occurs when bones are It is usually accompanied by sprains, inflammation, and joint immobilization. Dislocations may result from serious falls and are common contact sports injuries. Joints of the jaw, forced out of alignment.

most commonly dislocated. Like fractures, dislocations must be reduced; that is, the bone ends must be returned to shoulders, fingers, and

Cartilage Injuries

Many aerobics devotees, encouraged to "feel the burn" during their workout, may feel the snap and pop of their overstressed cartilage instead. Although most cartilage injuries involve tearing of the knee menisci, overuse damage to the articular cartilages becoming increasingly common in competitive young athletes. Cartilage is avascular and it rarely can obtain sufficient nourishment to repair itself; thus, it usuof other joints

The

day.

tiny lens

is

Because cartilage fragments (called loose bodies) can interfere with joint function by causing the joint to lock or bind, most sports physicians recommend that the central (nonvascular) part of a damaged cartilage be removed. Today, this can be done by arthroscopic surgery (ar-throskop'ik; "looking into joints"), a procedure that enables patients to be out of the hospital the same ally stays torn.

their proper positions

thumbs

are

by a physician. Subluxation

is

a partial dislocation of a joint.

Repeat dislocations of the same joint are combecause the initial dislocation stretches the

mon

joint capsule

and ligaments. The resulting loose

cap-

sule provides poor reinforcement for the joint.

Inflammatory and Degenerative Conditions Inflammatory conditions that affect joints include and various forms of arthritis.

bursitis, tendonitis,

Bursitis

and Tendonitis

inflammation of a bursa and is usually caused by a blow or friction. Falling on one's knee Bursitis

is

Chapter 8

may

273

Joints

result in a painful bursitis of the prepatellar

bursa,

known

as housemaid's

knee or water on the

knee. Prolonged leaning on one's elbows may damage the bursa close to the olecranon process, producing student's elbow, or olecranon bursitis. Severe cases are treated by injecting anti-inflammatory

drugs into the bursa.

removing some

fluid

If

excessive fluid accumulates,

by needle aspiration

may

re-

lieve the pressure.

Tendonitis is inflammation of tendon sheaths, caused by overuse. Its symptoms (pain and swelling) and treatment (rest, ice, and antiinflammatory drugs) mirror those of bursitis. typically

Arthritis

The term of

arthritis describes over

1

00

different types

inflammatory or degenerative diseases that dam-

age the joints. In all its forms, arthritis

is

the most

X

FIGURE 8.14 rheumatoid

ray of a hand

deformed by

arthritis.

widespread crippling disease in the United States. One out of seven Americans suffers its ravages. To a greater or lesser degree, all forms of arthritis have the

same

initial

symptoms: pain,

stiffness,

and swelling

of the joint.

i

1

Acute forms of arthritis usually result from bacterial invasion and are treated with antibiotics. The synovial membrane thickens and fluid production decreases, causing increased friction and pain. Chronic forms of arthritis include osteoarthritis, rheumatoid arthritis, and gouty arthritis. Osteoarthritis (OA) is the most A chronic (long-term) degenerative condition, is often called "wearand-tear arthritis." is most prevalent in the aged and is probably related to the normal aging process (although it is seen occasionally in younger people

Osteoarthritis chronic

common

arthritis.

OA

OA

and some forms have a genetic basis). More women than men are affected, but 85% of all Americans de-

This sound, called crepitus (krep'i-tus), results as the roughened articular surfaces rub together. The

most often affected and lumbar spine and the joints

and

are those of the cervical fingers, knuckles, knees,

hips.

The course irreversible. In

usually slow and

of osteoarthritis

is

many

symptoms

cases, its

are con-

with a mild pain reliever like aspirin or acetaminophen, along with moderate activity to keep the joints mobile. Magnetic therapy (assumed to stimulate the growth and repair of articular cartilage) is retrollable

ported to provide treated.

relief to

Glucosamine

about

70%

of patients

sulfate, a nutritional supple-

ment, appears to decrease pain and inflammation and may help to preserve the articular cartilage. Osteoarthritis is rarely crippling, but it can be, particularly when the hip or knee joints are involved.

velop this condition.

Current theory holds that normal joint use prompts the release of (metalloproteinase) enzymes that break down articular cartilage. In healthy individuals,

this

damaged

cartilage

is

eventually

with OA, more cartilage is destroyed than replaced. Although its specific cause is unknown, OA may reflect the cumulative effects of years of compression and abrasion acting at joint surfaces, causing excessive amounts of the cartilagedestroying enzymes to be released. The result is softened, roughened, pitted, and eroded articular replaced, but in people

Arthritis Rheumatoid arthritis (RA; roo'mah-toid) is a chronic inflammatory disorder with an insidious onset. Though it usually arises between the ages of 40 and 50, it may occur at any age. It affects three

While not as

times as

common

many women

as osteoarthritis,

as

men.

rheumatoid

arthritis causes disability in millions (Figure 8.14). It

occurs in more than 1% of Americans. In the early stages of RA, joint tenderness and stiffness are common. Many joints, particularly the

As the disease progresses, the exposed bone tissue thickens and forms bony spurs (osteophytes)

small joints of the fingers, wrists, ankles, and feet, are afflicted at the same time and bilaterally. For example, if the right elbow is affected, most likely the left elbow is also affected. The course of RA is vari-

bone ends and may restrict joint movement. Patients complain of stiffness on arising that lessens somewhat with activity. The affected joints may make a crunching noise as they move.

and marked by flare-ups (exacerbations) and remissions [rheumat = susceptible to change). Other manifestations include anemia, osteoporosis, muscle atrophy, and cardiovascular problems.

cartilages.

that enlarge the

I

Rheumatoid

able

274

Unit

A {CLOSER}

There

is

Movement

Covering, Support, and

II

LOO K y?

a stark contrast

From Knights

Joints:

between

Body

in

Shining

Armor to

it

and the modern development of joint prostheses (artificial joints). The great-

be engineered by modern-day visionaries and implanted

being tested

is

ROBODOC,

to

still

beneath.

protecting the Ironically,

protect were the

took

The

the body,

in

less

first

human

a

difficult to

quest that

than 60 years.

history of joint prostheses dates

to the 1940s

and 1950s, when World

ficial

II

limbs. Today, over a third of a mil-

a robotic drill

is

packed

cartilage.

surgeon,

a better-fitting hole

for the femoral prosthesis In

and the Korean War left large numbers of wounded who needed arti-

War

which

eroded

solution

to

in

a gel,

fit

the ball-and-

socket joints they found so

in

into an area of

making them so is a major goal. The problem is that the prostheses work loose over time, so researchers are seeking to enhance the

between implant and bone. One is to strengthen the cement that binds them (simply eliminating air bubbles from the cement increases its durability). Another solution currently

while

bility

Humans

active people, but

by visionary men of the Middle Ages and Renaissance was to design armor joints that allowed moest challenge faced

joints

Bionic

and placed

done to reduce pain and restore about 80% of original joint function. Replacement joints are not yet strong or durable enough for young, are

took to develop joints for medieval suits of armor the centuries

of the

hip surgery.

in

cementless prostheses, researchers

bone

are exploring ways to get the

grow so

that

implant.

A super-smooth

to

binds strongly to the

it

titanium

Americans receive total joint replacements each year, mostly because of the destructive effects of osteoarthritis or rheumatoid arthritis. To produce durable, mobile joints, a substance was needed that was strong, nontoxic, and resistant to the

coating seems to encourage direct

computer-aided manufacturing) techniques have significantly reduced the

These techniques offer hope for younger patients, since they could stave off the need for a joint prosthesis

corrosive effects of organic acids

time and cost of creating individualized

for several years.

lion

blood.

In

1963, Sir

bony on-growth. Dramatic changes are also occurring in

the way

in

John Charnley, an

joints.

joints are

artificial

CAD/CAM

patient's

X

rays

computer draws

English orthopedic surgeon, per-

ical

from a database of hundreds of normal joints and generates possible designs

arthritic hips. His

device consisted of a

stem and a cup-shaped polyethylene plastic socket anchored to the pelvis by methyl methacrylate cement. This cement proved to be exceptionally strong and relatively problem-free. Hip prostheses were followed by knee prostheses, but not until 10 years later did smoothly operating total knee joint replacements become a metal

ball

reality.

on

a

Today, the metal parts of the

prostheses are strong cobalt and

tita-

nium alloys, and the number of knee replacements equals the number of

many

other joints, including fingers,

el-

bows, and shoulders. Total hip and knee replacements

last

about 10 to 15 years

who do

stress the joint.

Most such operations

not excessively

Once

com-

puter produces a program to direct the

machines that shape it. Joint replacement therapy is coming of age, but equally exciting are techniques that call on the ability of the patient's ate,

such

own

tissues to regener-

a

way

Osteochondral grafting: Healthy bone and cartilage are removed from one part of the body and

joint.

grow rapidly and quickly begin synthesizing proteins and other molecules that chondroblasts produce. Clinical studies on animals are ongoing to determine if these

reprogrammed fat cells that look, walk, and talk like cartilage cells will continue to behave like them when implanted into the body.

Still

another treatment

Mesenchymal stem

is

the ap-

molecule called vasointestinal peptide (VIP) to alparent

ability of a signaling

ter the activity of the

immune

cells,

thus reducing inflammation and are

damage. However, human

still

And

in

cartitrials

the distant future.

so,

through the centuries, the

focus has shifted from jointed armor to artificial

joints that

can be put inside

the body to restore lost function.

in

cell

regenera-

mesenchymal removed from bone marrow

tion: Undifferentiated cells are

cartilage. Unlike

cartilage cells.rthese cells

joint.

Autologous chondrocyte implantation: Healthy chondrocytes are removed from the body, cultivated in the lab, and implanted at the

damaged

make

avenue being investigated

as:

found

to reprogram precursor fat cells

(stromal cells) to

lage

for

elderly patients

for a prosthesis.

selected, the

transplanted to the injured

hip replacements.

Replacements are now available

and modifications the best design

is

Additionally, researchers have

and med-

formed the first total hip replacement and revolutionized the therapy of

information, the

a hip prosthesis.

made.

(computer-aided design and

Fed the

Photograph of

Mod-

ern technology has accomplished what

the armor designers of the Middle

Ages never even dreamed

of.

Chapter 8

RA

—

an autoimmune disease a disorder in which the body's immune system attacks its own is

The

tissues.

initial

trigger

for

this

reaction

is

Gout

is far

more common

275

Joints

in males than in fe-

males because males naturally have higher blood levels of uric acid. Because gout seems to run in fam-

unknown, but the streptococcus bacterium and

ilies,

viruses have been suspect. Perhaps these microorganisms bear molecules similar to some naturally

Untreated gout can be very destructive; the articulating bone ends fuse and immobilize the joint. Fortunately, several drugs (colchicine, nonsteroidal anti-inflammatory drugs, glucocorticoids, and others) that terminate or prevent gout attacks are available. Patients are advised to avoid alcohol excess (which promotes uric acid overproduction), and foods high in purine-containing nucleic acids, such

present in the joints, and the immune system, once activated, attempts to destroy both.

RA

begins with inflammation of the synovial membrane [synovitis) of the affected joints. Inflammatory cells (lymphocytes, neutrophils, and others) migrate into the joint cavity from the blood and unleash a deluge of inflammatory chemicals that destroy body tissues when released inappropriately in large amounts as in RA. Synovial fluid accumulates, causing joint swelling and in time, the inflamed synovial membrane thickens into a pannus ("rag"), an abnormal tissue that clings to the articular cartilages. The pannus erodes the cartilage (and sometimes the underlying bone) and eventually scar tissue forms and connects the bone ends. Later this scar tissue ossifies and the bone ends fuse together, immobilizing the joint. This end condition, called ankylosis (ang'ki-lo'sis; "stiff condition"), often pro-

duces bent, deformed fingers (see Figure 8.14). Not all cases of RA progress to the severely crippling ankylosis stage, but all cases do involve restriction of joint

movement and extreme

A wonder drug for RA

pain.

sufferers

is still

undiscov-

Currently the pendulum is swinging from RA therapy utilizing aspirin, long-term antibiotic therapy, and physical therapy to a more progressive treatment course using anti-inflammatory drugs or immunosuppressants. Particularly promising are etanercept (Enbrel) and infliximab (Remicade), the first in a class of drugs called biologic response modifiers that neutralize some of ered.

conservative

the harmful properties of the inflammatory chemicals. Joint prostheses, if available, are the last resort for severely crippled RA patients (see A Closer Look).

Gouty

Uric acid, a normal waste product of nucleic acid metabolism, is ordinarily excreted in urine without any problems. However, when blood levels of uric acid rise excessively (due to its excessive production or slow excretion), it may be deposited as needle-shaped urate crystals in the soft tissues of joints. An inflammatory response folArthritis

as

genetic factors are definitely implicated.

liver,

kidneys, and sardines.

Developmental Aspects of Joints As bones form from mesenchyme in the embryo, the joints develop in parallel. By eight weeks, the synovial joints resemble adult joints in form and arrangement. Injuries aside, relatively few interferences

with middle age. Eventually advancing years do take their toll and ligaments and tendons shorten and weaken. The intervertebral discs become more likely to herniate, and osteoarthritis rears its ugly head. Virtually everyone has osteoarthritis to some degree by the time they are in their 70s. The middle years also see an increased incidence of rheumatoid arthritis. Exercise that coaxes joints through their full range of motion, such as regular stretching and aerobics, is the key to postponing the immobilizing effects of aging on ligaments and tendons, to keeping cartilages well nourished, and to strengthening the muscles that stabilize the joints. The key word for exercising is "prudently," because excessive or abusive use of the joints guarantees early onset of osteoarthritis. The buoyancy of water relieves much of the stress on weight-bearing joints, and people who swim or exercise in a pool often retain good joint function as long as they live. As with so many medical problems, it is easier to prevent joint problems than to cure or correct them. joint function occur until late

The importance

of joints is obvious:

ton's ability to protect other organs

smoothly

reflects their presence.

The

and

to

skele-

move

Now that we are fa-

gouty arthritis (gow'te), or gout. The initial attack typically affects one joint, often at the base of the

miliar with joint structure and with the movements that joints allow, we are ready to consider how the muscles attached to the skeleton cause body move-

great toe.

ments by acting across

lows, leading into an agonizingly painful attack of

its joints.

276

Unit

II

Movement

Covering, Support, and

of the

Body

Related Clinical Terms Ankylosing spondylitis (ang'kl-l6z"ing

=

crooked, bent; spondyl

=

vertebra)

spon"di-li'tis;

ankyl

A variant of rheuma-

toid arthritis that chiefly affects males;

it usually begins in the sacroiliac joints and progresses superiorly along the spine. The vertebrae become interconnected by fibrous tissue, causing the spine to become rigid ("poker back").

Arthrology

=

(ar-throl'o-je logos ;

study)

The study

of joints.

Chondromalacia patellae (kon-dro-mal-a'si-ah; "softening of cartilage by the patella") Damage and softening of the articular cartilages on the posterior patellar surface and the anterior surface of the distal femur; most often seen in adolescent athletes. Produces a sharp pain in the knee leg

is

extended

(in

climbing

stairs, for

example).

when

the

May result

when

the quadriceps femoris, the main group of muscles on the anterior thigh, pulls unevenly on the patella, persistently rubbing it against the femur in the knee joint; often corrected by exercises that strengthen weakened parts of the quadriceps muscles.

Rheumatism

A

term used by laypeople to indicate disease involving muscle or joint pain; consequently may be used to apply to arthritis, bursitis, etc. Synovitis (sin"o-vi'tis) Inflammation of the synovial memjoint. In healthy joints, only small amounts of

brane of a

synovial fluid are present, but synovitis causes copious amounts to be produced, leading to swelling and limitation of joint

movement.

Chapter Summary 1. Joints, or articulations, are sites where bones meet. Their functions are to hold bones together and to allow various de-

movement.

grees of skeletal

Classification of Joints

(p.

253)

They are classed functionally as synarthrotic, amphiarthrotic, or diarthrotic. (pp.

of muscles

253-254)

Fibrous joints occur where bones are connected by fibrous tissue; no joint cavity is present. Nearly all fibrous 1.

joints are synarthrotic.

Sutures/syndesmoses/gomphoses. The major types of fibrous joints are sutures, syndesmoses, and gomphoses. 2.

When

whose tendons

stabilizing factor in

cross the joint

many

Synovial Joints

(pp.

is

joints.

259-264)

muscle contracts, the insertion (movthe origin (immovable attachment). Three common types of movements can occur when muscles contract across joints: (a) gliding movements, 7.

or synovial.

Fibrous Joints

The tone

most important

Movements Allowed by

Joints are classified structurally as fibrous, cartilaginous,

1.

6.

the

a skeletal

able attachment)

moves toward

(b) angular movements (which include flexion, extension, abduction, adduction, and circumduction), and (c) rotation.

8. Special movements include supination and pronation, inversion and eversion, protraction and retraction, elevation and depression, and opposition.

Types of Synovial Joints

(pp.

264-266)

range of motion. Motion nonaxial (gliding), uniaxial (in one plane), biaxial (in two planes), or multiaxial (in all three planes). 9. Synovial joints differ in their

may be Cartilaginous Joints

(pp.

254-255)

1.

In cartilaginous joints, the bones are united by cartilage;

10.

no

joint cavity is present.

joints

Synchondroses/symphyses. Cartilaginous joints include synchondroses and symphyses. Synchondroses are synarthrotic,- all symphyses are amphiarthrotic. 2.

The

six

major categories of synovial

(movement

joints are plane

nonaxial), hinge joints (uniaxial), pivot

joints (uniaxial, rotation permitted), condyloid joints (biaxial with angular movements in two planes), saddle joints (biaxial, like condyloid joints, but wittafreer movement), and

ball-and-socket joints (multiaxial and rotational movement).

Synovial Joints 1.

Most body

(pp.

255-271)

joints are synovial joints, all of

Selected Synovial Joints

which

are di-

arthrotic.

General Structure

(pp.

255-256)

2. All synovial joints have a joint cavity enclosed by a fibrous capsule lined with synovial membrane and reinforced by ligaments, articulating bone ends covered with articular

cartilage,

and synovial

fluid in the joint cavity.

Some

(pp.

256-257)

Bursae are fibrous sacs lined with synovial membrane and containing synovial fluid. Tendon sheaths are similar to bursae but are cylindrical structures that surround muscle tendons. Both allow adjacent structures to move smoothly over one another. Factors Influencing the Stability of Synovial Joints

257-259)

5.

Ligaments prevent undesirable movements and

it.

12. The hip joint is a ball-and-socket joint formed by the acetabulum of the coxal bone and the femoral head. It is highly adapted for weight bearing. Its articular surfaces are deep and secure. Its capsule is heavy and strongly reinforced by ligaments.

rein-

The elbow

a hinge joint in which the ulna (and rawith the humerus, allowing flexion and extension. Its articular surfaces are highly complementary and are the most important factor contributing to joint stability.

13.

is

dius) articulates

14.

Articular surfaces providing the most stability have large surfaces and deep sockets and fit snugly together.

4

force the joint.

11. The shoulder joint is a ball-and-socket joint formed by the glenoid cavity of the scapula and the humeral head. The most freely movable joint of the body, it allows all angular and rotational movements. Its articular surfaces are shallow. Its capsule is lax and poorly reinforced by ligaments. The tendons of the biceps brachii and rotator cuff muscles help to stabilize

3.

(pp.

266—271)

(e.g.,

the knee) contain fibrocartilage discs that absorb shock.

Bursae and Tendon Sheaths

(pp.

The knee

joint

is

the largest joint in the body.

It is

a

hinge joint formed by the articulation of the tibial and femoral condyles (and anteriorly by the patella and patellar surface of the femur). Extension, flexion, and (some)

Chapter 8

rotation are allowed. Its articular surfaces are shallow and condyloid. C-shaped menisci deepen the articular surfaces. The joint cavity is enclosed by a capsule only on the sides and posterior aspects. Several ligaments help prevent displacement of the joint surfaces. Muscle tone of the quadri-

semimembranosus muscles

ceps and

important in knee

is

277

Joints

inflammation or degeneration accompanied by stiffness, pain, and swelling. Acute forms generally result from bacterial infection. Chronic forms include os5. Arthritis is joint

teoarthritis,

rheumatoid

6. Osteoarthritis is a

arthritis,

and gouty

arthritis.

degenerative condition most

in the aged. Weight-bearing joints are

most

common

affected.

stability.

Homeostatic Imbalances of Joints

(pp.

272-275)

joints.

Common

Joint Injuries

(p.

272) 8. Gouty arthritis, or gout, is joint inflammation caused by the deposit of urate salts in soft joint tissues.

Sprains involve stretching or tearing of joint ligaments. Because ligaments are poorly vascularized, healing is slow. 1.

Cartilage injuries, particularly of the knee, are common and may result from excessive twisting or

2.

7. Rheumatoid arthritis, the most crippling arthritis, is an autoimmune disease involving severe inflammation of the

in contact sports

Developmental Aspects of Joints

(p.

275)

1 Joints form from mesenchyme and in tandem with bone development in the embryo. .

high pressure.

The

avascular cartilage

is

unable to repair

itself.

Excluding traumatic injury, joints usually function well which time symptoms of connective tissue stiffening and osteoarthritis begin to appear. Prudent 2.

Dislocations involve displacement of the articular surfaces of bones. They must be reduced.

until late middle age, at

Inflammatory and Degenerative Conditions

exercise delays these effects, whereas excessive exercise pro-

3.

(pp.

motes the

272-275)

early onset of arthritis.

and tendonitis are inflammations of a bursa and tendon sheath, respectively.

4. Bursitis

a

Review Questions Short Answer Essay Questions

Multiple Choice/Matching

(Some questions have more than one correct answer. Select the best answer or answers from the choices given.) 1.

Match

Key:

(a)

fibrous joints

(c)

synovial joints

the key terms to the appropriate descriptions. cartilaginous joints

(b)

(3) (4)

10.

11. Joint

sutures and syndesmoses

bones connected by collagen fibers types include synchondroses and symphyses

13.

(7)

14.

fibrocartilage

joints.

are amphiarthrotic

movable

joints are

(a)

Anatomical characteristics (b)

synarthroses,

(b) di-

of a synovial joint include

a joint cavity,

(c)

an

(a)

articular capsule,

of these.

(c)

of these.

tone of surrounding muscles,

(d)

following description "Articular surfaces deep and secure,- capsule heavily reinforced by ligaments and muscle tendons; extremely stable joint" best describes (a) the elbow joint, (b) the hip joint, (c) the knee joint, (d) the shoulder joint.

—

means

6.

Ankylosis

7.

An autoimmune

twisting of the ankle, (b) tearing of ligaments, (c) displacement of a bone, (d) immobility of a joint due to fusion of its articular surfaces.

joint

(a)

disorder in which joints are affected biand which involves pannus formation and gradual

immobilization is (a) bursitis, rheumatoid arthritis.

tis, (d)

nonaxial, uniaxial, biaxial, or of these

terms means. of flexion

part of this description. 17.

Why

are sprains

and

cartilage injuries a particular

18. List the functions of the following elements of a synovial joint: fibrous part of the capsule, synovial fluid, articular disc.

—

The

laterally

what each

problem?

reinforcing ligaments,

5.

movements may be

16. The knee has been called "a beauty and a beast." Provide several reasons that might explain the negative (beast)

4. Factors that influence the stability of a synovial joint include (a) shape of articular surfaces, (b) presence of strong

all

lo-

15. What is the specific role of the menisci of the knee? of the anterior and posterior cruciate ligaments?

amphiarthroses.

articular cartilage,

body

How does rotation differ from circumduction? Name two types of uniaxial, biaxial, and multiaxial

many

(c)

common

1 2. Compare and contrast the paired movements and extension with adduction and abduction.

bones connected by a disc of hyaline cartilage or

2. Freely

the structure, function, and

multiaxial. Define

(8) nearly all are synarthrotic (9) shoulder, hip, jaw, and elbow joints

(d) all

Compare

(6)

arthroses,

joint.

9. Discuss the relative value (to body homeostasis) of immovable, slightly movable, and freely movable joints.

(5) all are diarthrotic

3.

Define

cations of bursae and tendon sheaths.

(1) exhibit a joint cavity (2) types are

8.

(b)

gout,

(c)

osteoarthri-

Critical

Thinking and

Clinical Application

Questions 1. Sophie worked as a cleaning woman for 30 years so she could send her two children to college. Several times, she had been forced to call her employers to tell them she could not come in to work because one of her kneecaps was swollen and painful. What is Sophie's condition, and what probably caused it?

278

Unit

II

Covering, Support, and

Movement

of the

jogging down the road, he tripped and his ankle twisted violently to the side. When he picked himself up, he was unable to put any weight on that ankle. The diagnosis was severe dislocation and sprains of the left ankle. The orthopedic surgeon stated that she would perform a closed reduction of the dislocation and attempt ligament repair by using arthroscopy, (a) Is the ankle joint normally a stable joint? (b) What does its stability depend on? (c) What is a closed reduction? (d) Why is ligament repair necessary? (e) What does arthroscopy entail? (f) How will the use of this procedure minimize Harry's recuperation time (and 2.

As Harry was

left

suffering) 3.

Mrs.

?

a 4 5 -year- old woman, appeared at her physicomplaining of unbearable pain in the distal in-

Bell,

cian's office

terphalangeal joint of her right great toe. The joint was red and swollen. When asked about previous episodes, she

Body

two years earlier that disappeared had come. Her diagnosis was arthritis, (a)

recalled a similar attack

suddenly as

it

What

(b)

type?

What

is

the precipitating cause of this partic-

ular type of arthritis?

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Muscles and Muscle Tissue

Overview of Muscle Tissues (pp. 280-281) 1.

Compare and

12. Describe factors that influence

the force, velocity, and

duration of skeletal muscle

contrast the

contraction.

basic types of muscle tissue. 2.

List four of

important functions

muscle

13. Describe three types of skeletal

muscle

tissue.

fibers

and explain the each type.

relative value of

Skeletal Muscle (pp. 3.

281-309)

14.

Describe the microscopic structure and functional roles of the myofibrils, sarcoplasmic

reticulum, and

muscle 5.

T

tubules of

Smooth Muscle (pp. 309-315) 15. Compare the gross and microscopic anatomy of

fibers (cells).

smooth muscle

Explain the sliding filament

skeletal

mechanism. 6.

Define motor unit and explain

how muscle

fibers are

cells to that of cells.

Compare and contrast the mechanisms and the means of activation of skeletal and smooth muscles.

Define muscle twitch and describe the events occurring

during 8.

16.

muscle

contractile

stimulated to contract. 7.

contrast the

and resistance exercise on skeletal muscles and on other body systems.

Describe the gross structure of a skeletal muscle.

4.

Compare and

effects of aerobic

its

between

unit and multiunit

three phases.

how smooth,

Explain

17. Distinguish

single-

smooth

muscle structurally and graded

functionally

contractions of a skeletal

muscle are produced. 9.

Developmental Aspects 318-319)

Differentiate between

of Muscles (pp.

isometric and isotonic

18. Describe

contractions. 10. Describe three

ATP

is

skeletal

11. Define

ways

in

which

regenerated during

muscle contraction.

oxygen debt and muscle

fatigue. List possible causes of

muscle

fatigue.

embryonic development of muscle tissues and the changes that occur in skeletal muscles with age.

280

Unit

II

Covering, Support, and

Movement

of the

Because flexing muscles look like mice scurrying beneath the skin, some scientist long ago dubbed them muscles, from the Latin mus meaning "little mouse." Indeed, the rippling muscles of professional boxers or weight lifters are often the first thing that comes to mind when one hears the word muscle. But muscle is also the dominant tissue in the heart and in the walls of other hollow organs. In all its forms, muscle tissue makes up nearly half the body's mass. The most distinguishing functional characteristic of muscles is their ability to transform chemical energy (ATP) into directed mechanical energy. In so doing, they become capable of exerting force.

Overview of Muscle Tissues

and smooth. Before exploring their characterishowever, let us introduce some terminology. First, skeletal and smooth muscle cells (but not cardiac muscle cells) are elongated and, for this reason, are called muscle fibers. Second, muscle contraction depends on two kinds of myofilaments, which are the muscle equivalents of the actin- or myosincontaining microfilaments described in Chapter 3.

diac, tics,

will recall, these

neural controls allow the heart to "shift into high gear" for brief periods, as when you race across the tennis court to make that overhead smash. Smooth muscle tissue is found in the walls of hollow visceral organs, such as the stomach, urinary

and respiratory passages. Its role is to force and other substances through internal body channels. It has no striations, and like cardiac muscle, it is not subject to voluntary control. We can describe smooth muscle tissue most precisely as visceral, nonstriated, and involuntary. Contractions of smooth muscle fibers are slow and sustained. Skeletal and smooth muscles are discussed in this chapter. Cardiac muscle is discussed in Chapter fluids

three types of muscle tissue are skeletal, car-

As you

and the same muscles can exert a force of about 70 pounds to pick up this book! Cardiac muscle tissue occurs only in the heart (the body's blood pump), where it constitutes the bulk of the heart walls. Like skeletal muscle cells, cardiac muscle cells are striated, but cardiac muscle is not voluntary. Most of us have no conscious control over how fast our heart beats. Key words to remember for this muscle type are cardiac, striated, and involuntary. Cardiac muscle usually contracts at a fairly steady rate set by the heart's pacemaker, but

bladder,

Types of Muscle Tissue The

Body

two proteins play

18 (The Heart). Table 9.3 on pp. 314-315 summarizes the most important characteristics of each type of

muscle

tissue.

a role in

motility and shape changes in virtually every cell in

Functional Characteristics

the body, but this property reaches its highest development in the contractile muscle fibers. Third,

of Muscle Tissue

whenever you see the prefixes myo or mys (both are word roots meaning "muscle") and sarco (flesh), the reference is to muscle. For example, the plasma membrane of muscle fibers is called the sarcolemma (sar"ko-lem'ah), literally "muscle" (sarco) "husk" (lemma), and muscle fiber cytoplasm is called sarcoplasm.

Now we

are ready to describe the three

types of muscle tissue.

Skeletal muscle tissue

is

packaged into the and cover the

skeletal muscles, organs that attach to

bony skeleton. Skeletal muscle fibers are the longest muscle cells; they have obvious stripes called striations and can be controlled voluntarily. Although it is often activated by reflexes, skeletal muscle is called voluntary muscle because it is the only type subject to conscious control. Therefore, when you think of skeletal muscle tissue, the key words to keep in mind are skeletal, striated, and voluntary. Skeletal muscle is responsible for overall body mobility. It can contract rapidly, but it tires easily and

must

rest after short periods of activity.

less, it

can exert tremendous power, a

by reports

is

tissue

is

endowed with some

tional properties that enable

it

to

Excitability, or irritability,

ceive

special func-

perform

is

its

duties.

the ability to

re-

and respond to a stimulus, that is, any change environment whether inside or outside the

in the

body. In the case of muscle, the stimulus

—

is

usually a

chemical for example, a neurotransmitter released by a nerve cell, or a local change in pH. The response is generation of an electrical impulse that passes along the sarcolemma (plasma membrane) of the muscle cell and causes the cell to contract. Contractility is the ability to shorten forcibly when adequately stimulated. This property sets muscle apart from all other tissue types. Extensibility is the ability to be stretched or extended. Muscle fibers shorten when contracting, but they can be stretched, even beyond their resting length,

when

Elasticity

and resume

relaxed. is

its

the ability of a muscle fiber to recoil

resting length after being stretched.

Neverthe-

fact revealed

of people lifting cars to save their loved

ones. Skeletal muscle

Muscle

also remarkably adaptable.

For example, your hand muscles can exert a force of a fraction of an ounce to pick up a dropped paper clip

Muscle Functions Muscle performs four important functions for the body: It produces movement, maintains posture, stabilizes joints, and generates heat.

Chapter 9

Muscles and Muscle Tissue

281

Producing Movement Just about all movements

of the human body and its muscle contraction. Skeletal muscles are responsible for all locomotion and manipulation. They enable you to respond quickly to

parts are a result of

changes in the external environment, for example, by jumping out of the way of a runaway car, directing your eyeballs, and smiling or frowning. The coursing of blood through your body is evidence of the work of the rhythmically beating cardiac muscle of your heart and the smooth muscle in the walls of your blood vessels, which helps maintain blood pressure. Smooth muscle in organs of the digestive, urinary,

and reproductive

tracts propels, or

substances (foodstuffs, urine, through the organs and along the tract. squeezes,

a

baby)

FIGURE 9.1 Photomicrograph of the capillary network surrounding skeletal muscle fibers. The supply was injected with dark red gelatin to demonstrate the capillary bed. The long muscle fibers are stained orange (30x). arterial

Maintaining Posture

We

are rarely aware of the workings of the skeletal muscles that maintain body posture. Yet these muscles function almost continuously, making one tiny adjustment after another that enables us to maintain an erect or seated posture despite the neverend-

ing

downward

present.

ments

A

skeletal muscle's shape

in the

and

body can be examined

its

easily

attach-

without

the help of a microscope.

pull of gravity.

Nerve and Blood Supply Stabilizing Joints

In general, each muscle

is

served by one nerve, an

Even as muscles pull on bones to cause movements, they stabilize and strengthen the joints of the skele-

or exit near the central part of the muscle

ton (Chapter

branch profusely through

8).

Generating Heat Finally muscles generate heat as they contract. This

heat is vitally important in maintaining normal body temperature. Because skeletal muscle accounts for at least 40% of body mass, it is the muscle type most responsible for generating heat. *

*

*

In the following section, we examine the structure and functioning of skeletal muscle in detail. Then we consider smooth muscle more briefly,

by comparing it with skeletal muscle. Because cardiac muscle is described in Chapter 1 8, its treatment in this chapter is limited to the summary largely

of its characteristics provided in Table 9.3.

artery,

and by one or more

veins, all of

which enter and

its connective tissue sheaths (described below). Unlike cells of cardiac and smooth muscle tissues, which can contract in the absence of nerve stimulation, each skeletal muscle fiber is supplied with a nerve ending that controls its activity.

Contracting muscle fibers use huge amounts of energy, a situation that requires

more

or less contin-

uous delivery of oxygen and nutrients via the arteries. Muscle cells also give off large amounts of metabolic wastes that must be removed through veins if contraction is to remain efficient. Muscle capillaries, the smallest of the body's blood vessels, are long and winding and have numerous cross-links, features that accommodate changes in muscle length (Figure 9.1). They straighten when the muscle is stretched and contort when the muscle contracts.

Connective Tissue Sheaths

Skeletal Muscle The

muscle organization, gross summarized in Table 9.1.

levels of skeletal

microscopic, are

to

sue sheaths support each cell and reinforce the muscle as a whole. We will consider these from internal

Gross Anatomy of a Skeletal Muscle Each skeletal muscle

is

a discrete organ,

several kinds of tissues. fibers

Although

made up

to external (Figure 9.2).

of

muscle nerve fibers, and skeletal

predominate, blood vessels, amounts of connective tissue are also

substantial

In an intact muscle, the individual muscle fibers are wrapped and held together by several different connective tissue sheaths. Together these connective tis-

1. Endomysium. Each individual muscle fiber is surrounded by a fine sheath of connective tissue consisting mostly of reticular fibers. This is the en-

domysium (en"do-mis'e-um; "within

the muscle").

282

Unit

Covering, Support, and

II

^

TABLE

9.1

Structure

and Organizational Level

Movement

of the

Body

Structure and Organizational Levels of Skeletal Muscle Connective

Muscle (organ)

Epimysium

Fascicle

(a

Tissue Wrappings

Description

Covered externally by

sands of muscle cells, plus connective tissue wrappings, blood vessels, and nerve fibers

the epimysium

Discrete bundle of muscle

Surrounded by perimysium

Tendon

Muscle

Fascicle

Consists of hundreds to thou-

portion of the muscle)

segregated from the rest of the muscle by a connective cells,

r

a

tissue sheath

Muscle

fiber

(cell)

Perimysium

Part of a fascicle

Muscle fiber

Elongated multinucleate

(cell)

has a

Nucleus

Endomysium

banded

Surrounded by the

eel

endomysium

(striated)

appearance

Myofibril .7

Part of a

muscle

•

*c-tc5» esa^atmeaofeatsf

Striations

fiber

Myofibril or fibril (complex organelle composed of bundles of myofilaments) Myofibril

Rodlike contractile element; myofibrils occupy most of the muscle cell volume; appear banded, and bands of adjacent myofibrils are aligned; composed of sarcomeres

arranged end to end

Sarcomere

s

_L

Sarcomere

(a

segment

of a myofibril)




(site of initial

local graded potential to action potential takes place

E

depolarization)

at the

rh

c

axon

potential

£o

hillock. In sensory neurons, the action

generated by the peripheral (axonal)

is

process just proximal to the receptor region. However, for simplicity, we will just use the term axon in

CL QJ

C

our discussion.

.a

E

Generation of an Action Potential Generating an action potential involves three consecutive

0)

-70 Resting potential

but overlapping changes in membrane permeability resulting from the opening and closing of active ion gates, all induced by depolarization of the axonal Distance (a few

FIGURE

11.11

produced by

Changes

in

a depolarizing

membrane

mm)

membrane

(Figure 11.12). Sequentially, these per+ meability changes are a transient increase in Na + permeability, followed by restoration of Na imper+ meability, and then a short-lived increase in K

potential

graded potential. Such

voltage changes are decremental because the current

permeability.

is

guickly dissipated by loss of ions through the "leaky" plasma

membrane. Consequently, graded

potentials are short-

distance signals.

The

first

permeability change

out within a few millimeters of its origin (Figure 11.11). Because the current dissipates quickly and dies out with increasing distance from the site of initial depolarization, graded potentials can act as signals only over very short distances. Nonetheless, they are essential in initiating action potentials, the

larization (the

is

The

principal

way neurons communicate

is

by

generating and propagating action potentials (APs), and for the most part, only cells with excitable

membranes

— neurons

and

muscle

cells

— can

generate action potentials. As illustrated in the graph in Figure 11.12, an action potential is a brief reversal of membrane potential with a total amplitude (change in voltage) of about 100 (from -70 to +30 mV). A depolarization phase is followed by a repolarization phase and often a short period of hyperpolarization. The whole event is over in a few milliseconds. Unlike graded potentials, action potentials do not decrease in strength with distance. The events of action potential generation and transmission are identical in skeletal muscle cells and neurons. In a neuron, an action potential is also called a nerve impulse, and only axons can generate one. A neuron transmits a nerve impulse only when it is adequately stimulated. The stimulus changes the permeability of the neuron's membrane by opening specific voltage-gated channels on the axon. These channels open and close in response to changes in the membrane potential and are activated

mV

mV

part of the

shown

AP

spike)

and

in the Figure 11.12

graph. Let's examine each of these phases more carefully

— we will

start

with a neuron in the resting

(polarized) state. (T)

Resting state: Voltage-gated channels closed. all

Na + and K + channels + amounts of K leave the cell

the voltage-gated

are closed, but, small

Action Potentials

oc-

responsible for both the repo-

downward

hyperpolarization phases

Virtually

long-distance signals.

two permeability changes

cur during the depolarization phase of action potential generation, indicated by the upward-rising part of the AP curve or spike of Figure 11.12. The third

via leakage channels Na + diffuse in.

and even smaller amounts

of

+

Each Na channel has two voltage- sensitive gates: an activation gate that is closed at rest and responds to depolarization by opening rapidly, and an inactivation gate that is open at rest and responds to depolarization by closing slowly. Thus, depolarization opens and then closes sodium channels. Both gates must be open in order for Na + to enter, but the closing of either gate effectively closes the channel. By contrast, each active potassium channel has a single voltage-sensitive gate;

it is

closed in the resting state

and opens slowly in response

to depolarization.

+ (D Depolarizing phase: Increase in Na permeability and reversal of membrane potential. As the

membrane

axonal

is

depolarized by local currents,

the

sodium channel activation gates open quickly

and

Na +

rushes into the cell. This influx of positive charge depolarizes that local "patch" of membrane further, cell

opening more activation gates so that the

interior

When

becomes progressively

less

negative.

depolarization at the stimulation site reaches

a certain critical level called threshold (often be-

tween -55 and -50 mV), depolarization becomes

Chapter 11

403

Fundamentals of the Nervous System and Nervous Tissue

Outside cell

Inside cell

(2)

Na + channels channels open K

(3) Repolarizing phase:

+ Depolarizing phase: Na channels open

closing and

+

Action potential

K + gates open

TO CD

tr

3

4

Time (ms) Potassium channel

Outside cell

Na +

•

Plasma

Outside

membrane

cell

activation gate

Inside cell

Sodium channel

inactivation gate

gated Na + and K + channels closed + (Na activation gates closed; inactivation gates open)

©Resting state:

All

FIGURE 11.12

Phases of the and the role of gated ion channels. The action action potential potential scan

in

the center of the

diagram can be divided into four phases, during which the voltagesensitive gates controlling

Na

+

+

+

K + channels remain open;

channels closed

sodium

channel gates have closed, but

(2) Depolarizing phase of the action

temporarily because the relatively slow

sodium gates are open, but potassium channels remain closed.

gates of those channels have not had time to respond to repolarization.

@

Repolarizing phase of the action

(4) Hyperpolarization: both

potassium channels remain open

Within another millisecond or two, the resting state (T)

sodium inactivation gates close the sodium channels, and

system

potassium channels open.

stimulus.

potential: )

Hyperpolarization:

(T) Resting state: neither channel is open. (Sodium inactivation gates are open, but activation gates are closed.)

potential:

and K channels are in different states and membrane permeability to sodium (P Na and potassium (P K is changing. )

@ Na

is

is

restored,

and the

ready to respond to the next

404

Unit

Regulation and Integration of the Body

Ml

self-generating, urged

on by

positive feedback.

That

being initiated by the stimulus, depolariza+ tion is driven by the ionic currents created by Na + influx. As more Na enters, the membrane depolar-

is,

after

izes further

and opens

still

more

activation gates +

Na +

channels are open. At this point, Na permeability is about 1000 times greater than in a resting neuron. As a result, the membrane potential becomes less and less negative and then overshoots + to about +30 as Na rushes in along its electrochemical gradient. This rapid depolarization and polarity reversal produce the sharply upward spike of the action potential (see the Figure 11.12 graph). until all

mV

Earlier,

we

stated that

membrane

potential de-

pends on membrane permeability, but here we are saying that membrane permeability depends on membrane potential. Can both statements be true? Yes, because these two relationships establish a pos+ itive feedback cycle (increased Na permeability due to increased channel openings leads to greater depo-

which

leads to increased

Na +

permeability, and so on). It is this explosive positive feedback cycle that is responsible for the rising (depolarizing) phase of action potentials and is the property that puts the "action" in the action potential. + Repolarizing phase: Decrease in Na permeability. The explosively rising phase of the action potential persists for only about 1 ms and is selflimiting. As the membrane potential passes 0 and becomes increasingly positive, the positive in+ tracellular charge resists further Na entry. In addi+ tion, the slow inactivation gates of the Na channels begin to close after a few milliseconds of depolariza+ tion. As a result, the membrane permeability to Na + declines to resting levels, and the net influx of Na stops completely. Consequently, the AP spike stops larization,

©

mV

rising

and reverses

direction.

+

Repolarizing phase: Increase in K permeabil+ ity. As Na entry declines, the slow voltage-sensitive + K gates open and K + rushes out of the cell, followelectrochemical gradient. Consequently internal negativity of the resting neuron is restored, an event called repolarization (see the Figure 11.12 + graph). Both the abrupt decline in Na permeability + and the increased permeability to K contribute to ing

its

repolarization.

+ Hyperpolarization: K permeability continues. Because potassium gates are sluggish gates that are slow to respond to the depolarization signal, the + period of increased K permeability typically lasts longer than needed to restore the resting state. (4)

As

a result of the excessive

K+

efflux,

an

after-

hyperpolarization, also called the undershoot, is seen on the AP curve as a slight dip following the spike (and before the potassium gates close). Notice that both the activation and inactivation

+

channels are closed during the gates of the Na after-hyperpolarization; hence the neuron is insensitive to a stimulus and depolarization at this time.

Although repolarization restores resting

electri-

does not restore resting ionic conditions. The ion redistribution is accomplished by the sodium-potassium pump following repolarization. While it might appear that tremendous num+ + bers of Na and K ions change places during action potential generation, this is not the case. Only small cal conditions,

amounts

of

it

sodium and potassium

cross the

mem-

+

Na influx required to reach threshold + produces only a 0.012% change in cellular Na concentration.) Because an axonal membrane has thou+ + sands of Na -K pumps, these small ionic changes

brane. (The

are quickly corrected.

Propagation of an Action Potential

If it is to

serve as the neuron's signaling device, an AP must be propagated (sent or transmitted) along the axon's entire length (Figure

1 1

.

13).

As we have

seen, the

AP

+

generated by the influx of Na through a given area of the membrane. This establishes local currents that depolarize adjacent membrane areas in the forward direction (away from the origin of the nerve impulse), which opens voltage-gated channels and triggers an action potential there. Because the area where the AP originated has just generated an action potential, the sodium gates in that area are closed and no new action potential is generated there. Thus, the AP propagates away from its point of origin. (If an isolated axon is stimulated by an electrode, or an axon is stimulated at a node of Ranvier, the nerve impulse will move away from the point of stimulus in all directions along the membrane.) In the body, action potentials are initiated at one end of the axon and conducted away from that point toward the axon's terminals. Once initiated, an action potential is self-propagating and continues along the axon at a constant velocity something is

—

like a

domino

effect.

Following depolarization, each segment of axonal membrane repolarizes, which restores the resting membrane potential in that region. Because these electrical changes also set up local currents, the repolarization wave chases the depolarization wave down the length of the axon. The propagation process just described occurs on unmyelinated axons. Propagation that occurs along myelinated axons, called saltatory conduction, is described shortly. Although the phrase conduction of a nerve impulse is commonly used, nerve impulses are not really conducted in the same way that an insulated wire conducts current. In fact, neurons are fairly poor conductors, and as noted earlier, local current flows decline with distance because the charges leak through the membrane. The expression propagation

—

I

FIGURE 11.13

Sodium gate

Closing

in

membrane—^ +

+

Open

(AP).

©—T*"*

An

Propagation of an action potential

action potential propagating along an axon at

0 ms, 1 ms, and 2 ms. The sodium gates are labeled closed, open, or closing. Small arrows indicate local currents

+30

r-

405

Fundamentals of the Nervous System and Nervous Tissue

Chapter 11

generated by the movement of positive

ions.

The

large

arrows indicate the direction of action potential propagation.

Not depicted, the current flows created by the opening of potassium channels (and subsequent repolarization) occur

c 0)

where sodium gates are shown as

o

a CD

closing.

—

c CD

n

i\

E

o

-55 -70

2

1

i— Threshold

of a nerve impulse is more accurate, because the action potential is regenerated anew at each mem4

3

brane patch, and every subsequent action potential is identical to that generated initially.

6

5

Distance along the axon (mm) (a)

Threshold and the All-or-None Not all local depolarization events potentials. The depolarization must values if an axon is to "fire." What

Time = 0 ms

Closed + + +

Open

Closing

+

+

©

r*"*i

Closed + + +

©

+

WHHHHHHHHtWMtW ±_©_L

+30

Phenomenon

produce action reach threshold determines the threshold point 7 One explanation is that threshold is the membrane potential at which the outward cur+ rent created by K movement is exactly equal to the + inward current created by Na movement. Threshold is typically reached when the membrane has been depolarized by 15 to 20 from the resting value. This depolarization status seems to represent an unstable equilibrium state at which one of two + things can happen. If one more Na enters, further + depolarization occurs, opening more Na channels and allowing more sodium ions entry. If, on the + other hand, one more K leaves, the membrane po+ tential is driven away from threshold, Na channels + close, and K continues to diffuse outward until the potential returns to its resting value. Recall that local depolarizations are graded .

i

mV

AP

— Threshold

r.

-55

-70 2

1

4

3

5

6

Distance along the axon (mm) (b)

Time =

1

ms

and that

potentials +

+30

Closed + +

+

Closing

+

++

©

+

Open

Closed +

©

T*"*Z

HtiBMBW ttfftff HKIffti

their

magnitude increases with

increasing stimulus intensity. Brief weak stimuli (subthreshold stimuli) produce subthreshold depothat are not translated into nerve impulses. On the other hand, stronger threshold stimuli produce depolarizing currents that push the larizations

membrane

potential toward and beyond the thresh-

old voltage.

As

a result,

Na +

permeability

is

in-

creased to such an extent that entering sodium ions

-55

r

41

"hreshold

-70

1

2

3

4

5

Distance along the axon (mm) (c)

Time = 2 ms

"swamp"

6

(exceed) the

outward movement of

K+

,

allowing the positive feedback cycle to become established and generating an action potential. The critical factor here is the total amount of current that flows through the membrane during a stimulus (electrical charge x time). Strong stimuli depolarize the membrane to threshold quickly. Weaker stimuli must be applied for longer periods to provide the crucial amount of current flow. Very weak stimuli do not trigger an action potential because the local current flows they produce are so slight that they dissipate long before threshold is reached.

'

406

Unit

Regulation and Integration of the Body

III

What causes

j?

after-hyperpolarization?

+30

c CD

I

lllllllll

0 i—Threshold

CD

1

I -55

llllllllllll

Absolute refractory period

i rJ

Relative refractory period

1

Depolarizatio

-70

'

.

I

I

Action potentia

1

(Na + enters)

t

y

it

1 t

+30

Time (ms)

\

—

c CD

*—>

O

ft

Q. CD

FIGURE 11.14

Relationship

Repolarization (K + leaves)

i

C

between stimulus

strength, local potential, and action potential frequency. Action potentials are shown as vertical

1—

£ -55 lines.

Upward arrows (t) indicate points of stimulus application; downward arrows (I) indicate stimulus cessation; arrow

CD

2

u

i

CO

.a

-70

- After-

t Resting

Stimulus

hyperpolarization

(undershoot) rhreshold

—

1

membrane

potential

—1

length indicates strength of stimulus. Notice that a

subthreshold stimulus does not generate an action potential but once threshold voltage stimulus, the

is

more frequently

2

1

4

3

reached, the stronger the

6

5

7

Time (ms)

action potentials are

generated.

FIGURE 11.15

Recording of an action potential

indicating the timing of the absolute and relative

The

action potential

is

an all-or-none phenom-

enon; it either happens completely or doesn't happen at all. Generation of an action potential can be compared to lighting a match under a small dry twig. The changes occurring where the twig is being heated are analogous to the change in membrane +

permeability that initially allows more Na to enter the cell. When that part of the twig becomes hot + enough (when enough Na has entered the cell), the

reached and the flame conif you blow out the action potential is generated and propagated whether or not the stimulus continues). But if the match is extinguished just before the twig has reached the critical temperature, ignition will not + take place. Likewise, if the number of Na entering the cell is too low to achieve threshold, no action flash point (threshold)

sumes the match (the

is

entire twig, even

potential will occur.

Coding for Stimulus Intensity

Once

refractory periods.

When

Refractory Periods

neuron membrane is generating an action potential and its sodium channels are open, the neuron cannot respond to another stimulus, no matter how strong. This period from the opening of the activation gates + of the Na channels to the closing of the inactivation gates, called the absolute refractory period (Figure 11.15), ensures that each action potential is a separate, all-or-none event and enforces one-way transmission of the action potential.

The

a patch of

relative refractory period

the interval

fol-

lowing the absolute refractory period. During the

rel-

ative refractory period,

Na +

is

gates are closed and

most have returned to their resting state, K + gates are open, and repolarization is occurring. During this time, the axon's threshold for

gener-

independent of stimulus strength, and all action potentials are alike. So how can the CNS determine whether a particular stimulus is intense or weak information it needs to initiate an appropriate response? The answer is really quite simple: Strong stimuli cause nerve impulses to be generated more often in a given time interval than do weak stimuli (Figure 11.14). Thus, stimulus intensity is coded for by the number of impulses generated per second that is, by the frequency of impulse transmission rather than by inated, all action potentials are

—

— —

creases in the strength (amplitude) of the individual action potentials.

tion

impulse genera-

A

threshold stimulus won't trigger an action potential during the relative refractory period, but an exceptionally strong stimu+ lus can reopen the Na gates and allow another impulse to be generated. Thus, by intruding into the is

substantially elevated.

relative refractory period, strong stimuli cause more frequent generation of action potentials.

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Fundamentals of the Nervous System and Nervous Tissue

Chapter 11

?

How does differ in a

the location of voltage-gated

myelinated axon

(as

Na

+

407

channels

depicted here) and

in

an unmyelinated axon?

Area

FIGURE 11.16

Saltatory conduction

in

a myelinated axon.

In

of

myelinated

nerve fibers, local currents (thin black arrows) give rise to a propagated action

and red arrows) that appears to jump from node to node. Notice that generated only at the nodes, the current flows along the axon from node to node. potential (pink

a

while action potentials are

Conduction Velocities

Conduction velocities of neurons vary widely. Nerve fibers that transmit impulses most rapidly (100 m/s or more) are found in neural pathways where speed is essential, such as those that mediate

some postural reflexes. Axons more slowly typically serve

that conduct impulses

internal organs (the gut, glands, blood vessels), where slower responses are not a handicap. The rate of impulse propagation depends largely on two factors: 1. Axon diameter. Axons vary considerably in diameter and, as a rule, the larger the axon's diameter, the faster it conducts impulses. This is because larger axons offer less resistance to the flow of local currents, and so adjacent areas of the membrane can more quickly be brought to threshold.

2.

Degree of myelination.

On unmyelinated axons,

action potentials are generated at sites immediately adjacent to each other and conduction is relatively slow, a type of AP propagation called continuous conduction. The presence of a myelin sheath dramatically increases the rate of impulse propagation

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because myelin acts as an insulator to prevent almost all leakage of charge from the axon. Current can pass through the membrane of a myelinated axon only at the nodes of Ranvier, where the myelin sheath is interrupted and the axon is bare, and + channels are essentially all the voltage-gated Na concentrated at the nodes. Thus, when an action potential is generated in a myelinated fiber, the local depolarizing current does not dissipate through the adjacent (nonexcitable) membrane regions but instead is maintained and moves to the next node, a distance of approximately 1 mm, where it triggers another action potential. Consequently, action potentials are triggered only at the nodes, a type of conduction called saltatory conduction [saltare = to leap) because the electrical signal jumps from node to node along the axon (Figure 11.16). Saltatory conduction is much faster than continuous conduction.

HOMEOSTATIC IMBALANCE The importance

myelin to nerve transmission is painfully clear to those with demyelinating diseases such as multiple sclerosis (MS). This autoimmune disease affects mostly young adults. Common symp-

toms

of

are visual disturbances (including blindness),

problems controlling muscles (weakness, clumsiness, and ultimately paralysis), speech disturbances,

408

Unit

Ml

Regulation and Integration of the Body

Axodendritic

Axosomatic synapses

synapses

Axon

(a)

FIGURE 11.17

Synapses,

and axoaxonic synapses,

(b)

(a)

Axodendritic, axosomatic,

Scanning electron micrograph

of incoming fibers at axosomatic synapses (4000X).

and urinary incontinence. In

this disease,

Axon

myelin

sheaths in the CNS are gradually destroyed, reduced to nonfunctional hardened lesions called scleroses. The loss of myelin (a result of the immune system's attack on myelin proteins) causes such substantial shunting and short-circuiting of the current that successive nodes are excited

more and more

Axosomatic synapses

slowly,

and eventually impulse conduction ceases. However, the axons themselves are not damaged and growing + numbers of Na channels appear spontaneously in the demyelinated fibers. This may account for the remarkably variable cycles of relapse (disability) and remission (symptom-free periods) typical of this

Soma of postsynaptic

neuron (b)

disease.

Until a few years ago,

could be done to help changing with the advent of the so-called disease-modifying drugs including interferon beta- la and -lb, Avonex, Betaseran, and Copaxone. These drugs seem to hold the symptoms at bay, reducing complications and the disability that often occurs with MS. •

MS

little

victims. This situation

Nerve

may be

is

based on diameter, degree of myelination, and conduction speed. Group A fibers are mostly somatic sensory and motor fibers serving the skin, skeletal muscles, and joints. They have the largest diameter and thick myelin sheaths, and conduct impulses at speeds ranging up to 150 m/s (over 300 mph). Autonomic nervous system

motor

fibers

classified

fibers serving the visceral organs; visceral sensory fibers; and the smaller somatic sensory fibers transmitting afferent impulses from the skin (such

belong in the B and C fiber groups. Group B fibers, lightly myelinated fibers of intermediate diameter, transmit impulses at an average rate of 15 m/s (about 40 mph). Group C fibers have the smallest diameter and are unmyelinated. Hence, they are incapable of saltatory conduction and conduct impulses at a leisurely pace 1 m/s (2 mph) or less. as pain

and small touch

fibers)

—

^(J)^

HOMEOSTATIC IMBALANCE

A number

and physical factors impair impulse propagation. Although their mechanisms of action differ, alcohol, sedatives, and injected anesthetics all block nerve impulses by reducing membrane permeability to ions, mainly Na + As we have + seen, no Na entry no action potential. of chemical

.

—

.

Chapter 11

Fundamentals of the Nervous System and Nervous Tissue

409

Cold and continuous pressure interrupt blood circulation (and hence the delivery of oxygen and nutrients) to neuron processes, impairing their ability to conduct impulses. For example, your fingers get numb when you hold an ice cube for more than a few seconds, and your foot "goes to sleep" when you sit on it. When you remove the cold object or pressure, impulses are transmitted again, leading to an unpleasant prickly feeling.

•

The Synapse system depends on the flow of information through chains of neurons functionally connected by synapses. A synapse (sin'aps), from the Greek syn, "to clasp or join," is a junction that mediates information transfer from one neuron it's to the next or from a neuron to an effector cell where the action is. Synapses between the axonal endings of one neuron and the dendrites of other neurons are axodendritic synapses (Figure 11.17). Those between axonal endings of one neuron and cell bodies of other neurons are axosomatic synapses. Less

The operation

of the nervous

—

common

FIGURE 11.18

Freeze-fracture image of an electrical synapse in an adult rat hippocampus. The dark spheres are immunogold labels for the protein connexin36, which is

(and far less understood) are synapses between axons (axoaxonic), between dendrites (dendrodendhtic) or between dendrites and cell bodies

the

(dendrosomatic)

John Rash,

,

first connexin established as present in CNS electrical synapses (gap junctions) (200,000x). Photograph courtesy of

Ph.D.;

Colorado State

University.

The neuron conducting impulses toward the synapse is the presynaptic neuron and the neuron transmitting the electrical signal away from the synapse is the postsynaptic neuron. At a given

neuron is the information sender, and the postsynaptic neuron is the information receiver. As you might anticipate, most neurons function both as presynaptic and postsynaptic neurons. Neurons have anywhere from 1000 to 10,000 axonal terminals making synapses and are stimulated by an equal number of other neurons. In the body periphery, the postsynaptic cell may be either another neuron or an effector cell (a muscle synapse, the presynaptic

cell or

gland

cell).

electrical

Synapses

Electrical synapses, the less

common variety,

corre-

spond to the gap junctions found between certain other body cells (Figure 11.18). They contain protein channels, made of connexin subunits, that connect the cytoplasm of adjacent neurons and allow ions to flow directly from one neuron to the next. Neurons joined in this way are said to be electrically coupled, and transmission across these synapses is very rapid.

Depending on the nature

munication

may be

synchronizing the activity of all interconnected neurons. They appear to be important in CNS arousal from sleep and in mental attention and conscious perception. In adults, electrical synapses are found in regions of the brain responsible for cer-

of the synapse,

com-

unidirectional or bidirectional.

movements, such as the normal movements of the eyes, and in axoaxonic

tain stereotyped jerky

There are two varieties of synapses: and chemical. These are described next. Electrical

A key feature of electrical synapses between neurons is that they provide a simple means of

synapses in the hippocampus, a region intimately involved in emotions and memory. They are far more abundant in embryonic nervous tissue, where they permit exchange of guiding clues during early neuronal development so that neurons can connect properly with one another. As the nervous system develops, some electrical synapses are replaced by chemical synapses. Electrical synapses also exist between glial cells of the CNS, where they play a role in ion and water homeostasis.

Chemical Synapses In contrast to electrical synapses, which are specialized to allow the flow of ions between neurons,

410

Unit

III

Regulation and Integration of the Body

chemical synapses are specialized

for release

A

reception of chemical neurotransmitters.

and

typical

©

Neurotransmitter binds to postsynaptic

ceptors.

The neurotransmitter

re-

diffuses across the

chemical synapse is made up of two parts: (1) a knoblike axonal terminal of the presynaptic neuron,

synaptic cleft and binds reversibly to specific protein receptors clustered on the postsynaptic membrane.

which contains many

Ion channels open in the postsynaptic membrane. As the receptor proteins bind neurotransmitter molecules, the three-dimensional shape of the proteins changes. This causes ion channels to open, and the resulting current flows produce local changes in the membrane potential. Depending on

tiny,

membrane-bounded

called synaptic vesicles, each containing

of neurotransmitter molecules;

and

mitter receptor region on the

membrane

(2)

sacs

thousands

a neurotransof a den-

body of the postsynaptic neuron. Although close to each other, presynaptic and postsynaptic membranes are always separated by the synaptic cleft, a fluid-filled space approximately 30 to 50 nm (about one-millionth of an inch) wide. Because the current from the presynaptic membrane dissipates in the fluid-filled cleft, chemical synapses effectively prevent a nerve impulse from being directly transmitted from one neuron to another. drite or the cell

transmission of signals across these synapses is a chemical event that depends on the release, diffusion, and receptor binding of neurotransmitter molecules and results in unidirectional communication between neurons. Thus, while transmission of nerve impulses along an axon and across electrical synapses is a purely electrical event, chemical synapses convert the electrical signals to chemical signals (neurotransmitters) that travel across the synapse to the postsynaptic cells, where they are converted back into electrical signals. Instead,

Information Transfer Across Chemical Synapses When a nerve impulse reaches the axonal terminal, it sets into motion a chain of events that triggers neurotransmitter

release.

The neurotransmitter

on binding to recepon the postsynaptic membrane, causes changes

crosses the synaptic cleft and, tors

in the postsynaptic

shown Calcium channels open

steps are (T)

membrane

permeability.

The

in Figure 11.19:

in the presynaptic ax-

onal terminal. When the nerve impulse reaches the axonal terminal, membrane depolarization opens + 2+ channot only Na channels but voltage-gated Ca 2+ gates are nels as well. During the brief time the Ca 2+ open, Ca floods into the terminal from the extracellular fluid.

(D Neurotransmitter

Ca

2+

is

released.

The

surge of

into the axonal terminal acts as an intracellumessenger, directing docked synaptic vesicles to fuse with the axonal membrane and empty their contents by exocytosis into the synaptic cleft. The Ca 2+ is then quickly removed from the terminal, either taken up into the mitochondria or ejected from 2+ the neuron by an active Ca pump. The precise Ca 2+ sensor that initiates neurotransmitter exocyto2+ sis is still a question, but a Ca -binding protein called synaptotagmin found in the synaptic vesicles

lar

seems

a likely candidate.

(4)

the receptor protein to

which the neurotransmitter

binds and the type of channel the receptor controls, the postsynaptic neuron may be either excited or inhibited.

For each nerve impulse reaching the presynaptic terminal, many vesicles (perhaps 300) are emptied into the synaptic cleft. The higher the impulse fre-

quency

(that

greater the spill their

is,

the

number

more intense

the stimulus), the

of synaptic vesicles that fuse and

contents, and the greater the effect on the

postsynaptic

cell.

Termination of Neurotransmitter Effects

As

long as it is bound to a postsynaptic receptor, a neurotransmitter continues to affect membrane permeability and to block reception of additional "messages" from presynaptic neurons. Thus, some means of "wiping the postsynaptic slate clean" is necessary. The effects of neurotransmitters last a few milliseconds before being terminated by one of three mechanisms. Depending on the particular neurotransmitter, the terminating mechanism may be 1. Degradation by enzymes associated with the postsynaptic membrane or present in the synapse. This is the case for acetylcholine.

Reuptake by astrocytes or the presynaptic terminal, where the neurotransmitter is stored or destroyed by enzymes, as with norepinephrine. 2.

3. Diffusion

away from the synapse.

Although some neurons can transmit impulses at 150 m/s (300 mph), neural transmission across a chemical synapse is comparatively slow and reflects the time required for

Synaptic Delay

neurotransmitter release, diffusion across the synapse, and binding to receptors. Typically, this synaptic delay which lasts 0.3-5.0 ms, is the ratelimiting (slowest) step of neural transmission. Synaptic delay helps explain why transmission along short neural pathways involving only two or three neurons occurs rapidly, but transmission along multisynaptic pathways typical of higher mental functioning occurs much more slowly. However, in practical terms these differences are not noticeable.

-

Chapter 11

Why may such

-

Fundamentals of the Nervous System and Nervous Tissue

411

axonal terminals be referred to as "bio-

logical transducers"?

Neurotransmitter

Receptor

FIGURE 11.19 Events at a chemical synapse in response to depolarization. (?) Arrival of the wave (nerve impulse) opens calcium channels and allows 2+ influx into the axonal terminal. Ca depolarization

(5) Synaptic vesicles fuse with the

presynaptic

neurotransmitter

@

is

Many receptors

present on postsynaptic membranes at chemical synapses are specialized to open ion channels, thereby converting chemical signals to electrical signals.

Unlike the voltage-gated ion chan-

nels responsible for action potentials, however, these

chemically gated channels are relatively insensitive to changes in membrane potential. Consequently, channel opening at postsynaptic membranes cannot

become

self-amplifying or self-generating.

Instead, neurotransmitter receptors mediate local

changes in

membrane potential that are graded acthe amount of neurotransmitter released

cording to and the time tials are

voltage changes

in

that

membrane.

@

Neurotransmitter

is

quickly destroyed by

enzymes present

at

the synapse or taken

back

into the presynaptic terminal;

depletion of neurotransmitter closes the ion channels

and terminates the

synaptic response.

membrane and

Postsynaptic Potentials and Synaptic Integration

possibly

released into the

The neurotransmitter diffuses across the synaptic cleft and attaches to receptors on the postsynaptic membrane. (4) Binding of neurotransmitter opens ion channels in the postsynaptic membrane, resulting in synapse.

remains in the area. Action potencompared with postsynaptic potentials in it

Excitatory Synapses and EPSPs At excitatory synapses, neurotransmitter binding causes depolarization of the postsynaptic membrane. However, in contrast to what happens on axonal membranes, only a single type of channel opens on postsynaptic membranes (those of dendrites and + neuronal cell bodies). This channel allows Na and + K to diffuse simultaneously through the membrane in opposite directions. Although this two-way cation flow may appear to be self-defeating when depolarization

is

remember that the electrochemisodium is much steeper than that for

the goal,

cal gradient for

+

+

potassium. Hence, Na influx is greater than K efflux, and net depolarization occurs. If enough neurotransmitter binds, depolarization of the postsynaptic membrane can successfully

Table 11.2.

Chemical synapses are either excitatory or inhibitory, depending on how they affect the membrane potential of the postsynaptic neuron.

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2 01 luajjno /eoupa/a ue tuojj \eu6\s auj

a6ueip /auj asneoag

y

412

Unit

„ >

III

Regulation and Integration of the Body

postsynaptic neuron. Although currents created by individual EPSPs decline with distance, they can and often do spread all the way to the axon hillock. If currents reaching the hillock are strong enough to depolarize the axon to threshold, axonal voltage-

+30

E.

0

i

gated channels open and an action potential

Threshold —

is

generated. \f

Inhibitory Synapses and IPSPs Time (ms)

20

10

Excitatory postsynaptic potential (EPSP)

(a)

Binding of neurotransmitters at inhibitory synapses reduces a postsynaptic neuron's ability to generate an action potential. Most inhibitory neurotransmitters induce hyperpolarization of the postsynaptic membrane by making the membrane more permeable to K + and/or Cl Sodium ion permeability is not af+ + channels are opened, K moves out of fected. If K the cell; if Cl channels are opened, Cl~ moves in. In either case, the charge on the inner face of the membrane becomes more negative. As the membrane po.

Threshold

and is driven farther from the axon's postsynaptic neuron becomes less and threshold, the less likely to "fire" and larger depolarizing currents tential increases

\

(b) Inhibitory

are required to induce

Time (ms)

20

10

postsynaptic potential (IPSP)

an action potential. Such

changes in potential are called inhibitory postsynaptic potentials (IPSPs) (see Figure

FIGURE

1 1

.20

Postsynaptic potentials,

excitatory postsynaptic potential (EPSP)

depolarization of the postsynaptic

is

(a)

that brings the

neuron closer to threshold for AP generation. It is mediated by neurotransmitter binding that opens channels allowing + + the simultaneous passage of Na and K through the postsynaptic

membrane,

potential results

in

(b)

An

inhibitory postsynaptic

hyperpolarization of the postsynaptic

neuron and drives the neuron away from the threshold for It is mediated by neurotransmitter binding that opens

firing.

K

+

or Cl~ gates or both.

The red

vertical

1.20b).

An

a local

membrane

1

arrows represent

stimulation.

Integration and Modification of Synaptic Events

Summation by the Postsynaptic Neuron single

EPSP cannot induce an action potential

A in the

postsynaptic neuron. But if thousands of excitatory axonal terminals are firing on the same postsynaptic membrane, or if a smaller number of terminals are delivering impulses rapidly, the probability of reach-

ing threshold depolarization increases greatly. Thus,

EPSPs can add

together, or

summate,

to influence

the activity of a postsynaptic neuron (Figure 11.21).

Nerve impulses would never be

my

which is well above an axon's threshold reach 0 (about —50 mV) for "firing off" an action potential. However, postsynaptic membranes do not generate action potentials; only axons (with their voltagegated channels) have this capability. The dramatic polarity reversal seen in axons never occurs in membranes containing only chemically gated chan+ and nels because the opposite movements of K Na + prevent accumulation of excessive positive charge inside the cell. Hence, instead of action potentials, local graded depolarization events called excitatory postsynaptic potentials (EPSPs) occur at excitatory postsynaptic membranes (see Figure 11.20a). Each EPSP lasts a few milliseconds and then the membrane returns to its resting potential. The only function of EPSPs is to help trigger an action potential distally at the axon hillock of the

not

initiated

if

this were

so.

Two types of summation occur. Temporal summation occurs when one or more presynaptic neurons transmit impulses in rapid-fire order and bursts of neurotransmitter are released in quick succession.

The

impulse produces a slight EPSP, and before successive impulses trigger more EPSPs. These summate, producing a much greater it

first

dissipates,

depolarization of the postsynaptic

would

result

from

membrane than

a single EPSP.

occurs when the postsynaptic neuron is stimulated at the same time by a large number of terminals from the same or, more commonly, different neurons. Huge numbers of its receptors bind neurotransmitter and simultaneously initiate EPSPs, which summate and dramatically enSpatial

summation

hance depolarization.

— Chapter 11

413

Fundamentals of the Nervous System and Nervous Tissue

> E Threshold of axon of postsynaptic neuron

c d)

o Q.

Resting

fs

asneoag

overlie

sulci

divide each hemisphere into

five

and inthe cranial bones that

frontal, parietal, temporal, occipital,

but the

them

last

named for

(Figure

12.6a).

The

central sulcus,

Chapter 12

435

The Central Nervous System

Central sulcus Precentral gyrus

Postcentral gyrus Parietal lobe

Frontal lobe

Parieto-occipital sulcus

on medial surface hemisphere)

of

Lateral sulcus

Occipital lobe

Temporal lobe Transverse cerebral fissure

Cerebellum

Pons Medulla oblongata Spinal cord

Anterior

- Frontal

Longitudinal

lobe

fissure

White matter Fissure (a

Cerebral veins

deep sulcus)

and

arteries

Parietal lobe

covered by arachnoid

Left cerebral

Right

hemisphere

cerebral

hemisphere Occipital

lobe

Posterior (b)

Left cerebral

hemisphere

Cerebellum

Brain stem-

(c)

FIGURE 12.6 of the lobes

Lobes and fissures of the cerebral hemispheres,

and major

cerebral hemispheres,

(a) Diagram and fissures of the brain, (b) Superior surface of the Photograph of the left lateral view of the brain.

sulci (c)

436

Unit

III

Regulation and Integration of the Body

sensations, to communicate, remember, and under-

Central sulcus

and to initiate voluntary movements. Because composed of gray matter, the cerebral cortex consists of neuron cell bodies, dendrites, and unmyelinated axons (plus associated glia and blood vessels), but no fiber tracts. It contains billions of neurons arranged in six layers, and accounts for stand,

it

0

is

40%

of total brain mass. Although it is only (about 1/8 inch) thick, its many convolutions effectively triple its surface area. In the late 1800s, anatomists mapped subtle

roughly

2-4

mm

variations in the thickness and structure of the cere-

Most

successful in these efforts was K. Brodmann, who in 1906 produced an elaborate

bral cortex.

numbered mosaic Longitudinal

Left frontal

Left

fissure

lobe

lobe

Areas active in speech and

temporal

hearing (fMRI)

Brodmann

now called map emerging,

of 52 cortical areas,

With

areas.

a structural

were eager

early neurologists

to localize functional

Modern imaging techshow maximal metabolic

regions of the cortex as well.

FIGURE

niques 12.7

Functional neuroimaging of the cerebral

cortex. The rostral direction

is

to the

left.

Functional magnetic

resonance image (fMRI) of the cerebral cortex of a person speaking and hearing reveals

activity

(blood flow)

in

— PET

activity in the brain, or functional

reveal blood flow (Figure 12.7) specific

the

scans to

MRI

— have

motor and sensory functions

to

that

are localized in

discrete cortical areas called domains.

posterior frontal and superior temporal lobes, respectively.

scans

shown

However,

many which lies in the frontal plane, separates the frontal lobe from the parietal lobe. Bordering the central sulcus are the precentral gyrus anteriorly and the postcentral gyrus posteriorly. More posteriorly the occipital lobe is separated from the parietal lobe by the parieto-occipital sulcus (pah-ri"e-to-ok-sip'i-tal), located

on the medial surface

The deep

of the hemisphere.

temporal lobe and separates it from the overlying and frontal lobes. A fifth lobe of the cerebral hemisphere, the insula fin'su-lah "island"), is buried deep within the lateral sulcus and forms part of its floor. The insula is covered by portions of the temporal, parietal, and frontal lobes. The cerebral hemispheres fit snugly in the skull. ;

Rostrally, the frontal lobes lie in the anterior cranial

The

anterior parts of the temporal lobes

fill

the

middle cranial fossa. The posterior cranial fossa, however, houses the brain stem and cerebellum; the occipital

lobes are located well superior to that cranial fossa.

Each

cerebral

hemisphere

has

three

regions: a superficial cortex of gray matter,

bered in Figure 12.8. Before we examine the functional regions of the cerebral cortex, let's consider some generalizations about this region of the brain: 1.

lateral sulcus outlines the flaplike

parietal

fossa.

higher mental functions, such as memory and language, appear to have overlapping domains and are spread over large areas of the cortex. Some of the most important Brodmann areas are num-

basic

which

looks gray in fresh brain tissue; an internal white matter; and the basal nuclei, islands of gray matter situated deep within the white matter. We consider

The

cortex contains

cerebral

three kinds of

functional areas: motor areas, sensory areas, and

as-

As you read about these areas, do not confuse the sensory and motor areas of the cortex with sensory and motor neurons. All neurons in

sociation areas.

the cortex are interneurons.

Each hemisphere is chiefly concerned with the sensory and motor functions of the opposite (con2.

tralateral) side of

the body.

Although largely symmetrical in structure, the two hemispheres are not entirely equal in function. 3.

Instead, there

a lateralization (specialization) of

is

cortical functions. 4.

The

final,

and perhaps most important,

ization to keep in

mind

is

general-

that our approach

is

a

no functional area of the cortex acts alone, and conscious behavior involves

gross oversimplification;

the entire cortex in one

way or

another.

these regions next.

Motor Areas

Cerebral Cortex

The

cerebral cortex is the "executive suite" of the nervous system, where our conscious mind is found. It enables us to be aware of ourselves and our

As shown in Figure 12.8a, the motor areas of the cortex, which control voluntary movement, lie in the posterior part of the frontal lobes: primary motor cortex, premotor corfollowing

tex, Broca's area,

and the frontal eye

field.

437

The Central Nervous System

Chapter 12

What anatomical landmark separates motor areas of

1

the cerebral cortex from sensory areas? Central sulcus

Primary motor area

Primary somatosensory cortex

Premotor cortex

- Somatic

Somatosensory

sensation

association cortex Frontal

eye

field

Gustatory cortex

Taste

Working memory for spatial

Wernicke's area (outlined by dashes)

tasks

Executive area for task

General interpretation area (outlined by dots)

management

Broca's

area

Working memory

Primary visual for

cortex

object-recall tasks

- Vision

Visual

association

complex multi-task problems Solving

area

Auditory

Prefrontal cortex

association area

- Hearing Primary auditory area (a)

Premotor Primary motor area

cortex

Corpus Central sulcus

callosum

Primary somatosensory cortex

Frontal

eye

field

Parietal lobe

Somatosensory

Prefrontal

association area

cortex

Parieto-occipital

Area

for

sulcus

mentalization Occipital

lobe

Processes emotions related to personal

and social interactions

Visual association

area Orbitofrontal

cortex

Olfactory bulb

Primary

Uncus

visual cortex

Olfactory tract (b)

Fornix

Parahippocampal

Olfactory areas

gyrus

FIGURE 12.8 Functional and structural areas of the cerebral cortex, (a) Lateral view, left cerebral hemisphere. Different colors define functional regions of the cortex.

The

olfactory area, which

is

deep

medial hemispheric surface, indicate

Brodmann

to the temporal lobe is

not identified.

structural areas,

whereas colors and

outlines represent functional regions of the cortex, 'sno/ns /ejjua^

(b) Parasagittal view, right

on the

Numbers

hemisphere.

438

Unit

Why

Regulation and Integration of the Body

III

are the

motor and sensory homunculi

anatomically "disformed"?

FIGURE amount

12.9

Motor and sensory areas of the cerebral cortex. The

of cortical tissue devoted to each function

is

indicated by the

the gyrus occupied by the body diagrams. The primary motor cortex precentral gyrus

is

postcentral gyrus

represented on the

is

left,

represented on the

ramidal tracts, or corticospinal tracts (kor"ti-kospi'nal). All other descending motor tracts issue from brain stem nuclei and consist of chains of two or more neurons. The entire body is represented spatially in the primary motor cortex of each hemisphere. In other

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aqj

ui

esse

ai/j

edje

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oj pa;eo

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of

the

and the somatic sensory cortex

Large neurons, called pyramidal cells, in these gyri allow us to consciously control the precise or skilled voluntary movements of our skeletal muscles. Their long axons, which project to the spinal cord, form the massive voluntary motor tracts called the py-

g

amount in

the

right.

1. Primary (somatic) motor cortex. The primary motor cortex is located in the precentral gyrus of the frontal lobe of each hemisphere (Brodmann area 4).

-/pap xajjco jejqajao

in

relative

moveand those that control hand movements are in another. Such a mapping of the body in CNS structures is called somatotopy

words, the pyramidal

ments

cells that control foot

are in one place

(so"mah-to-to'pe).

As

illustrated in Figure 12.9, the

—

body is typically represented upside down with the head at the inferolateral part of the precentral gyrus, and the toes at the superomedial end. Most of the neurons in these gyri control muscles in body areas having the most precise motor control that is, the face, tongue, and hands. Consequently, these regions of the caricature-like motor homunculis (ho-mung'ku-lis; singular = homunculus; "little man") drawn in Figure 12.9 are shown disproportionately large. The motor innervation of the body is contralateral; that is, the left primary motor gyrus controls muscles on the right side of the body, and

—

vice versa.

Chapter 12

The motor homunculus view of the primary motor cortex, shown at the left in Figure 12.9, imone-to-one correspondence between certain cortical neurons and the muscles they control, but this is somewhat misleading. Current research indicates that a given muscle is controlled by multiple spots on the cortex and that individual cortical neurons actually send impulses to more than one muscle. In other words, individual motor neurons control muscles that work together in a synergistic way to perform a given movement. For example, reaching forward with one arm involves some muscles acting at the shoulder and some acting at the elbow. Thus, instead of the discrete map offered by the motor homunculus, the primary motor cortex map is an orderly but fuzzy map with neurons arranged in useful ways to control and coordinate sets of muscles. Neurons controlling the arm, for instance, are intermingled and overlap with those controlling the hand and shoulder. However, neurons controlling unrelated movements, such as those controlling the arm and those controlling body trunk muscles, do not cooperate in motor activity. Thus, the motor homunculus is useful to show that broad areas of the primary cortex are devoted to the leg, arm, torso, and head, but neuron organization within those broad areas is much more diffuse than initially imagined. plies a

2.

Premotor cortex.

(Brodmann area

premotor cortex (see Figure

12.8).

6) is

the

This region con-

learned motor skills of a repetitious or pat-

terned nature, such as playing a musical instrument

and typing. The premotor cortex coordinates the movement of several muscle groups either simultaneously or sequentially mainly by sending activating impulses to the primary motor cortex. However, the premotor cortex also influences motor activity more directly by supplying about 1 5% of pyramidal tract fibers.

Think

skilled

motor

of this region as the

memory bank

for

activities.

This region also appears to be involved in planning movements. Using highly processed sensory information received from other cortical areas, it can control voluntary actions that depend on sensory feedback, such as moving an arm through a maze to grasp a hidden object. Broca's area (bro'kahz). Broca's area lies anterior to the inferior region of the premotor area and over3.

Brodmann

44 and 45. It has long been considered to be 1 present in one hemisphere only (usually the left) and (2) a special motor speech area laps

areas (

)

that directs the muscles involved in speech production.

"light

However, recent studies using PET scans to up" active areas of the brain indicate that

Broca's area also

many

speak and even as we think about (plan) voluntary motor activities other than speech. 4.

Frontal eye

field.

The

frontal eye field

is

located

partially in and anterior to the premotor cortex

and

superior to Broca's area. This cortical region controls

voluntary

movement

of the eyes.

HOMEOSTATIC IMBALANCE

**(Dk

Damage

primary motor paralyzes the body muscles

to localized areas of the

cortex (as from a stroke) controlled by those areas.

If

the lesion

is

in the right

hemisphere, the left side of the body will be paralyzed. Only voluntary control is lost, however, as the muscles can still contract reflexively. Destruction of the premotor cortex, or part of it,

motor

results in a loss of the

skill(s)

programmed

in

that region, but muscle strength and the ability to

perform the discrete individual movements are not hindered. For example, if the premotor area controlling the flight of your fingers over a computer keyboard were damaged, you couldn't type with your usual speed, but you could still make the same movements with your fingers. Reprogramming the skill into another set of premotor neurons would require practice, just as the initial learning process did.

•

Just anterior to the precentral

gyrus in the frontal lobe trols

439

The Central Nervous System

becomes

active as

we

prepare to

Sensory Areas

Areas concerned with conscious awareness of sensation, the sensory areas of the cortex, occur in the parietal, temporal, and occipital lobes (see Figure 12.8). 1.

Primary somatosensory cortex. This cortex

re-

sides in the postcentral gyrus of the parietal lobe, just posterior to the

mann

areas 1-3).

primary motor cortex (Brod-

Neurons

in this gyrus receive

information from the general (somatic) sensory receptors in the skin and from proprioceptors in skeletal muscles. The neurons then identify the body region being stimulated, an ability called spatial discrimination. As with the primary motor cortex, the body is represented spatially and upsidedown according to the site of stimulus input, and the right hemisphere receives input from the left side of

the body.

The amount

particular

body region

sitivity (that

is,

to

of sensory cortex devoted to a is

related to that region's sen-

how many receptors

it

has),

not to

humans, the face (esfingertips are the most sensiand

the size of the body region. In pecially the lips) tive

body

areas;

hence these are the

the somatosensory half of Figure 12.9. 2.

largest parts of

homunculus shown

in the right

Somatosensory association cortex. The

so-

matosensory association cortex lies just posterior to the primary somatosensory cortex and has many

440

Unit

III

Regulation and Integration of the Body

connections with it. The major function of this area is to integrate sensory inputs (temperature, pressure,

and so forth) relayed to it via the primary somatosensory cortex to produce an understanding of an object being felt: its size, texture, and the relationship of its parts. For example, when you reach into your pocket, your somatosensory association cortex draws upon stored memories of past sensory experiences to perceive the objects you feel as coins or keys. Someone with damage to this area could not recognize these objects without looking at them. Visual areas. The primary visual (striate) cortex is seen on the extreme posterior tip of the occipital lobe, but most of it is buried deep in the calcarine sulcus (Figure 12.8b) in the medial aspect of the occipital lobe. The largest of all cortical sensory areas, the primary visual cortex receives visual information that originates on the retina of the eye. There is a contralateral map of visual space on the primary visual cortex, analogous to the body map on the 3.

somatosensory cortex.

The visual association area surrounds the primary visual cortex and covers much of the occipital lobe. Communicating with the primary visual cortex,

the visual association area uses past visual expe-

riences to interpret visual stimuli (color, form,

and

movement), enabling us to recognize a flower or a person's face and to appreciate what we are seeing. We do our "seeing" with these cortical neurons. However, recent experiments on monkeys indicate that complex visual processing involves the entire

nasal cavities send impulses along the olfactory tracts that are ultimately relayed to the olfactory cortices. The outcome is conscious awareness of differ-

ent odors. The olfactory cortex

is

part of the primitive

rhinencephalon (ri"nen-sef'ah-lon; "nose brain"), which includes all parts of the cerebrum that re-

—

the orbitofrontal cortex, ceive olfactory signals associated regions located on or in and the uncus the medial aspects of the temporal lobes, and the protruding olfactory tracts and bulbs that extend to the nose. During the course of evolution, most of the "old" rhinencephalon has taken on new functions

concerned chiefly with emotions and memory. This "newer" emotional brain, called the limbic system, is considered later in this chapter. The only portions of the human rhinencephalon still devoted to smell are the olfactory bulbs and tracts (described in Chapter 13) and the greatly reduced olfactory cortices.

Gustatory

The

gustatory cortex (gus'tah-tor-e) (see Figure 12.8a), a region involved in the perception of taste stimuli, is located in the 6.

(taste) cortex.

parietal lobe just deep to the temporal lobe. Logically,

it

occurs at the tip of the tongue of the

somatosensory homunculus. Vestibular (equilibrium) cortex. It has been difficult to pin down the part of the cortex responsible for conscious awareness of balance, that is, of the position of the head in space. However, medical imaging studies now locate this region in the posterior part of the insula, deep to the temporal lobe. 7.

posterior half of the cerebral hemispheres. Particu-

—

important are two visual "streams" one running along the top of the brain and handling object identity, the other taking the lower road and focusing larly

Damage

on

object locations.

4.

Auditory areas. Each primary auditory cortex

is

located in the superior margin of the temporal lobe

abutting the lateral sulcus. Sound energy exciting the inner ear hearing receptors causes impulses to be transmitted to the primary auditory cortex, where they are related to pitch, rhythm, and loudness. The more posterior auditory association area then permits the perception of the sound stimulus, which we "hear" as speech, a scream, music, thunder, noise, and so on. Memories of sounds heard in the past appear to be stored here for reference. Wernicke's area, described on the next page, is also part of the auditory cortex. 5. Olfactory (smell) cortex. Each olfactory cortex is found in a small area of the frontal lobe just above the orbit., and in the medial aspect of the temporal

lobe in a small region called the piriform lobe

HOMEOSTATIC IMBALANCE

which

is dominated by the hooklike uncus (Figure 12.8b). Afferent fibers from smell receptors in the superior

primary visual cortex results in functional blindness. By contrast, those with damage to the visual association area can see, but they do not comprehend what they are looking at. • to the

Association Areas

An

association area is any have the word primary in its name. As already described, the primary somatosensory cortex and each of the special sensory cortices have nearby association areas with which they communicate. These association areas, in turn, communicate ("associate") with the motor cortex and with other sensory association areas to analyze and act on sensory inputs in the light of past experience. Each association area has multiple inputs and outputs quite independent of the primary sensory and motor areas, indicating that their function is complex indeed. The remaining association areas, not connected with any of the sensory cortices, are cortical area that doesn't

described next.

i

Chapter 12

Prefrontal cortex. The prefrontal cortex, in the anterior portion of the frontal lobe (Figure 12.8b), is 1.

the most complieated cortical region of all. It is involved with intellect, complex learning abilities (called cognition), recall,

and personality.

It is

neces-

sary for the production of abstract ideas, judgment,

reasoning, persistence, long-term planning, concern

and conscience. That these qualities dein children implies that the prefrontal slowly velop cortex matures slowly and is heavily dependent on positive and negative feedback from one's social en-

acid in the

man beings

apart from other animals.

Tumors or other

may cause mental and ing mood swings and ness,

personality disorders includloss of judgment, attentive-

and inhibitions. The affected individual

about personal appearance, or rashly attacking a 7-foot opponent rather than running. careless

2.

Language areas.

A

large continuous area for

language comprehension and articulation surrounds the lateral sulcus in the left hemisphere,

which

is

hemisphere. The bestknown parts of this area are: (1) Wernicke's area (Figure 12.8a), formerly believed to be responsible for understanding written and spoken language, but now thought to be primarily involved in sounding out unfamiliar words; (2) Broca's area for speech prothe

language-dominant

duction;

(3)

the lateral prefrontal cortex, involved in

language comprehension and word analysis; and (4) most of the lateral and ventral parts of the temporal lobe,

which coordinate the auditory and visual

pects of language as

when naming objects

and

it

splashes

on you. You

see

So the traditional story goes

— but some modern

sources are abandoning this idea of a multisensory interpretation area or at least confining it to a much smaller region near the top and back of Wernicke's area. This change in theory reflects newer studies indicating that most of the relevant area is involved in the processing of spatial relationships. 4.

Visceral association area.

may be

The

cortex of the in-

involved in conscious perception of visstomach, full bladder, and the

ceral sensations (upset

like). However, a small part of the insular cortex functions in language.

may

becoming

be oblivious to social restraints, perhaps

lab

—

sula

lesions of the prefrontal cortex

chem

the bottle shatter,- hear the crash; feel your skin burning; and smell the acid fumes. However, these individual perceptions do not dominate your consciousness. What does is the overall message "danger" by which time your leg muscles are propelling you to the safety shower.

for others,

vironment. This cortex is closely linked to the emotional part of the brain (limbic system) and plays a role in intuitive judgments and mood. It is the tremendous elaboration of this region that sets hu-

441

The Central Nervous System

as :

or reading.

Lateralization of Cortical Functioning We use both cerebral hemispheres for almost every activity, and the hemispheres appear nearly identical. Nonetheless, there is a division of labor, and each hemisphere has unique abilities not shared by its partner. This phenomenon is called lateralization. Although one cerebral hemisphere or the other "dominates" each task, the term cerebral domi-

nance designates the hemisphere that is dominant for language. In most people (about 90%), the left hemisphere has greater control over language abilities, math, and logic. This so-called dominant hemisphere is working when we compose a sentence, balance a checkbook, and memorize a list. The other hemisphere (usually the right) is more free-spirited, involved in visual-spatial skills, intuition,

emotion, and

artistic

and musical

skills. It is

(This is only part of the story, but you've probably heard enough.)

the poetic, creative, and the "Ah-ha!" (insightful) side of our nature, and it is far better at recognizing

The corresponding areas in the right or nonlanguage-dominant hemisphere are involved in "body language" the nonverbal emotional (affec-

faces.

—

tive)

components

of language.

These areas allow the

or tone of our voice and our gestures to express our emotions when we speak, and permit us to comprehend the emotional content of what we hear. For example, a soft melodious response to your question conveys quite a different meaning than a sharp reply. lilt

General (common) interpretation area. The is an ill-defined region encompassing parts of the temporal, parietal, and occipital lobes. It is found in one hemisphere only, usually the left. This region receives input from all sensory association areas and integrates incoming signals into a single thought or understanding of the situation. Suppose, for example, you drop a bottle of 3.

general interpretation area

Most

individuals with

left

cerebral

dominance

are right-handed.

In the remaining 1 0% of people, the roles of the hemispheres are reversed or the hemispheres share

functions equally. Typically, right-cerebralare left-handed and male. Some "lefties" who have a cerebral cortex that functions bilaterally are ambidextrous. In other cases, however, this phenomenon results in cerebral confusion ("Is it your turn, or mine?") and learning disabilities, such as the reading disorder dyslexia, in which otherwise intelligent people may reverse the order of letters in words (and the order of words in sentences). their

dominant people

The two

and almost instantaneous communication with one another via connecting fiber tracts, as well as comcerebral hemispheres have perfect

plete functional integration. Furthermore, although

442

Unit

How

Regulation and Integration of the Body

III

can you explain the observation that the two

cerebral hemispheres have instantaneous tion with (b)

each other when

it is

communica-

obvious from diagram

that the projection fibers are part of crossed path-

ways and that information flows from each side of the

body

to only

one

(the opposite)

hemisphere?

Association fibers

Projection

-

fibers

—

^-Thalamus and

:

..

«*-^.jg^^M^ A^nF^r

/^C^ : x. -

-^•>=======^. Ar\

c>

—

Bl00d

Glands

vessel

Adrenal medulla

/|v

Acetylcholine

^jf

division

muscle (e.g., in

a blood

(. Acetylcholine

Parasympathetic

>4I

Ganglion

Autonomic nervous system

Smooth

/#

«

---

jb-

Sympathetic

Norepinephrine

v

— fife-

- -

-^v/.

Ganglion Key:

«™=

Preganglionic axons (sympathetic)

---=

Postganglionic axons (sympathetic)

FIGURE 14.2 Comparison of somatic and autonomic nervous systems. Somatic Division: Axons of somatic motor neurons extend from the CNS to their effectors (skeletal muscle cells). These axons are typically heavily myelinated. Somatic motor neurons release acetylcholine, and the effect is always stimulatory.

Autonomic

Division:

Axons

of

most

Myelination

to synapse

in

a peripheral

CNS

motor division lacks ganglia

A

few sympathetic preganglionic axons synapse with cells of the adrenal medulla. Postganglionic axons run from the ganglion to effectors (cardiac and smooth muscle fibers and glands). Preganglionic axons are lightly myelinated; postganglionic axons are All

preganglionic fibers

release acetylcholine;

The

all

---=

Preganglionic axons (parasympathetic)

autonomic

ganglion with a ganglionic neuron.

unmyelinated.

preganglionic neurons run from the

«—=

parasympathetic

Postganglionic axons (parasympathetic)

postganglionic fibers release acetylcholine;

most sympathetic

postganglionic fibers release norepinephrine. Stimulated adrenal

medullary

cells release

norepinephrine

and epinephrine into the blood. Autonomic effects are stimulatory or inhibitory, depending on the postganglionic neurotransmitter released and the receptor types on the effector organs.

root ganglia are part of the sensory, not the motor, division of the PNS.

Neurotransmitters released onto visceral effector organs by postganglionic autonomic fibers include norepinephrine (NE) secreted by most sympathetic fibers, and ACh released by parasympathetic fibers.

Neurotransmitter Effects

Depending on the type

motor neurons release acetylcholine (ACh) at their synapses with skeletal muscle fibers. The effect is always excitatory, and if stimulation reaches threshold, the muscle fibers contract.

target organ (Figure 14.2

entirely.

dorsal

All somatic

the organ's response

of receptors present

and Table 14.3 on

may

on the

p. 543),

be either excitation or

inhibition.

Overlap of Somatic and

Autonomic Function (jsodj 3Lft

oi /ejs/p saij

seajauM 'uoijBueB oiuuouoine

uoijBueB uoxe suojnau oiuo\\BueB

ai/j

pue SND

aoueisip sip sueds uojnau oiuoijBueBdjd aqj

uaa/w;aq

p

uoxe

dij±

Higher brain centers regulate and coordinate both somatic and autonomic motor activities, and nearly all spinal nerves (and many cranial nerves) contain both somatic and autonomic fibers. Moreover, most of the

534

Unit

Regulation and Integration of the Body

III

Not

body's adaptations to changing internal and external conditions involve both skeletal muscle activity and enhanced responses of certain visceral organs. For example, when skeletal muscles are working hard, they

as obvious, but equally characteristic, are changes in brain wave patterns and in the electrical resistance of the skin (galvanic skin resis-

need more oxygen and glucose and so autonomic mechanisms speed up heart rate and breathing to meet these needs and maintain homeostasis. The ANS is only one part of our highly integrated nervous system, but according to convention we will consider it an individual entity and describe its role

examinations.

mobilization.

tance)

During any type

control

in isolation in the sections that follow.

ANS

energy. Let's elaborate on these functional differences by focusing briefly on situations in which each is

exerting primary control.

detector

of vigorous physical activity, the

blood vessels are constricted, and blood is shunted to active skeletal muscles and the vigorously working heart. The bronchioles in the lungs dilate, increasing ventilation (and ultimately increasing oxygen deliv-

needs of

and the

cells),

into the blood to

The two arms of the ANS, the parasympathetic and sympathetic divisions, generally serve the same visceral organs but cause essentially opposite effects. If one division stimulates certain smooth muscles to contract or a gland to secrete, the other division inhibits that action. Through this dual innervation, the two divisions counterbalance each other's activities to keep body systems running smoothly. The sympathetic division mobilizes the body during extreme situations, whereas the parasympathetic arm performs maintenance activities and conserves body

lie

sympathetic division also promotes a number of other adjustments. Visceral (and perhaps cutaneous)

ery to body

Divisions

division

— events that are recorded during

body

liver releases

more glucose

accommodate the increased energy At the same time, temporarily

cells.

nonessential activities, such as gastrointestinal tract

damped. If you are running from a mugger, digesting lunch can wait! It is far more important that your muscles be provided with everything they need to get you out of danger. The sympathetic division generates a head of steam that enables the body to cope with situations motility, are

function is to provide the optimal conditions for an appropriate response to some threat, whether that response is to run, to see better, or to think more clearly. An easy way to remember the most important roles of the two ANS divisions is to think of the parasympathetic division as the division [digestion, defecation, and diuresis (urination)], and the sympathetic division as the E division (exercise, excitement, emergency, embarrassment). Remember, however, while it is easiest to think of the two ANS that threaten homeostasis.

Its

D

Role of the Parasympathetic Division

The parasympathetic

sometimes called the "resting and digesting" system, keeps body energy use as low as possible, even as it directs vital "housekeeping" activities like digestion and elimination of feces and urine. (This explains why it is a good idea to relax

division,

heavy meal: so that digestion is not interfered with by sympathetic activity.) Parasympathetic activity is best illustrated in a person who relaxes after a meal and reads the newspaper. Blood pressure, heart rate, and respiratory rate are regulated at low normal levels, the gastrointestinal tract is actively digesting food, and the skin is warm (indicating that there is no need to divert blood to skeletal muscles or vital organs). In the after a

eyes, the pupils are constricted to protect the retinas

from excessive

light,

and the lenses are accommo-

dated for close vision.

all- or- none fashion, this dynamic antagonism exists beand fine adjustments are made

divisions as working in an is

rarely the case.

tween the

A

divisions,

continuously by both.

ANS Anatomy The sympathetic and parasympathetic

divisions are

distinguished by 1. Their unique origin sites: Parasympathetic fibers emerge from the brain and sacral spinal cord (are

craniosacral); sympathetic fibers originate in the tho-

racolumbar region of the spinal cord.

The relative lengths of their fibers: The parasympathetic division has long preganglionic and short postganglionic fibers; the sympathetic division has the opposite condition. 2.

Role of the Sympathetic Division

The sympathetic "fight- or- flight"

we

division

system.

is

often referred to as the

Its activity is

are excited or find ourselves in

evident

when

emergency or

threatening situations, such as being frightened by street toughs late at night. A pounding heart; rapid, deep breathing; cold, sweaty skin; and dilated eye pupils are sure signs of sympathetic nervous system

3.

The

location of their ganglia:

Most parasympa-

thetic ganglia are located in the visceral effector or-

gans; sympathetic ganglia

lie

close to the spinal cord.

These and other differences are summarized in Table 14.1 and illustrated in Figure 14.3.

Chapter 14

TABLE

14.1

The Autonomic Nervous System

535

Anatomical and Physiological Differences Between the Parasympathetic and Sympathetic Divisions

J

Characteristic

Origin

Parasympathetic

Sympathetic

Craniosacral outflow: brain nuclei of cranial nerves

Thoracolumbar outflow: segments T,-L 2

stem

III, VII, IX, and X; segments S 2 -S 4

Ganglia

Location of ganglia

in

lateral

horn of gray matter of spinal cord

spinal cord

(intramural) or

close to visceral organ served

Ganglia within a few centimeters of CNS: alongside vertebral

column column

(chain or paravertebral ganglia)

and anterior to vertebral

(collateral or prevertebral ganglia)

Long preganglionic; short postganglionic

Short preganglionic; long postganglionic

and postganglionic fibers Rami communicantes

None

Gray and white rami communicantes. White rami contain myelinated preganglionic fibers; gray contain unmyelinated

Relative length of pre-

postganglionic fibers

Minimal

Degree of branching of

Extensive

preganglionic fibers Functional role

Neurotransmitters

Maintenance functions;

Prepares body to cope with emergencies and intense muscular

conserves and stores energy

activity

All fibers

release

ACh

(cholinergic fibers)

All

preganglionic fibers release ACh; most postganglionic fibers

release norepinephrine (adrenergic fibers); postganglionic fibers

serving sweat glands and some blood vessels of skeletal muscles release ACh; neurotransmitter activity augmented by release of

adrenal medullary hormones (norepinephrine and epinephrine)

Parasympathetic (Craniosacral) Division begin our exploration of the ANS with the anatomically simpler parasympathetic division. Because its preganglionic fibers spring from opposite ends of the CNS the brain stem and the sacral region of the spinal cord the parasympathetic divi-

We

—

sion

is

—

also called the craniosacral division (Figure

The

preganglionic axons extend from the the way to the structures to be innervated. There the axons synapse with ganglionic neurons located in terminal ganglia that lie very 14.4).

CNS

nearly

all

close to or within the target organs.

Very short post-

from the terminal ganglia and cells in their immediate area.

ganglionic axons issue

synapse with effector

Cranial

Outflow

Preganglionic fibers run in the oculomotor, facial,

glossopharyngeal, and vagus cranial nerves. Their cell bodies lie in associated motor cranial-nerve

FIGURE 14.3 ANS.

Overview of the subdivisions of the

and major organs served Synapse sites indicate the relative locations of the sympathetic and parasympathetic ganglia. Sites of origin of their nerves

are indicated.

Parasympathetic

Sympathetic

536

Unit

Regulation and Integration of the Body

III

nuclei in the brain stem (see Figures 12.15 and 12.16). The precise locations of the neurons of the cranial parasympathetics are described next.

Eye Lacrimal

s

Oculomotor nerves

1.

fibers of the

mucosa

Submandibular and sublingual

The parasympathetic

(III).

oculomotor nerves innervate smooth

muscles in the eyes that cause the pupils to constrict and the lenses to bulge actions needed to focus on close objects. The preganglionic axons found in the oculomotor nerves issue from the accessory oculomo-

—

tor (Edinger-Westphal) nuclei in the midbrain.

The

bodies of the ganglionic neurons are in the ciliary ganglia within the eye orbits (see Table 13.2, p. 502). cell

glands

2.

Facial nerves (VII).

The parasympathetic

fibers

of the facial nerves stimulate many large glands in the head. Fibers that activate the nasal glands and the lacrimal glands of the eyes originate in the lacrimal nuclei of the pons. The preganglionic fibers synapse with ganglionic neurons in the pterygopala-

tine ganglia (ter"eh-go-pal'ah-tin) just posterior to the maxillae. The preganglionic neurons that stimulate

the

submandibular and sublingual salivary

glands originate in the superior salivatory nuclei of the pons and synapse with ganglionic neurons in the submandibular ganglia, deep to the mandibular Liver

and

angles (see Table 13.2, p. 504).

gallbladder

3.

Glossopharyngeal nerves

(IX).

The parasympa-

thetics in the glossopharyngeal nerves originate in

Stomach

the inferior salivatory nuclei of the medulla and synapse in the otic ganglia, located just inferior to the foramen ovale of the skull.

The

postganglionic

and activate the parotid salivary glands anterior to the ears (see Table 13.2). Cranial nerves III, VII, and IX supply the entire parasympathetic innervation of the head, however only the preganglionic fibers lie within these three pairs of cranial nerves postganglionic fibers do not. The distal ends of the preganglionic fibers "jump over" to branches of the trigeminal nerves (V) to synapse; then the postganglionic fibers travel in the trigeminal nerves to reach the face. This "hitchhiking" takes advantage of the fact that the trigeminal nerves have the broadest facial distribution of all the cranial nerves and are well suited for this "delivery" role to the widely separated glands and smooth muscles in the head. fibers course to

Pancreas

Large intestine

Pelvic

splanchnic nerves

Small intestine

Hypogastric plexus

—

4. Urinary

Genitalia (penis,

clitoris,

lines indicate

and

tion of the parasympathetic cranial outflow

vagus

and vagina)

postganglionic

fibers.

organ. (Note:

Terminal ganglia

pelvic splanchnic nerve fibers are not

shown; most of these ganglia are located

CN =

cranial nerve.)

in

The remaining and major

bladder

FIGURE 14.4 Parasympathetic (craniosacral) division ANS. Solid lines indicate preganglionic nerve fibers. Dashed

(X).

and ureters

of the

of the vagus

Vagus nerves

or on the target

(X)

nerves.

is

por-

via the

Between them, the two vagus

nerves account for about 90% of all preganglionic parasympathetic fibers in the body. They provide fibers to the neck and to nerve plexuses (interweaving networks of nerves) that serve virtually every organ in the thoracic and abdominal cavities. The vagal nerve fibers (preganglionic axons) arise mostly from the dorsal motor nuclei of the medulla and synapse in terminal ganglia usually located in the

)

Chapter 14

Most terminal

walls of the target organ.

ganglia are

not individually named; instead they are collectively called intramural ganglia, literally "ganglia within the walls." As the vagus nerves pass into the thorax, they send branches to the cardiac plexuses supplying fibers to the heart that slow heart rate, the pulmonary plexuses serving the lungs and bronchi, and the esophageal plexuses (e-sof"ah-je'al) supplying

When the main trunks

of the

vagus nerves reach

the esophagus, their fibers intermingle, forming the anterior and posterior vagal trunks, each contain-

from both vagus nerves. These vagal

trunks then "ride" the esophagus down to the abdominal cavity. There they send fibers through the large aortic plexus [formed by a number of smaller plexuses (e.g., celiac, superior mesenteric, and hypogastric) that run along the aorta] before giving off branches to the abdominal viscera. The vagus nerves innervate the liver, gallbladder, stomach, small intestine, kidneys, pancreas, and the proximal half of the large intestine.

Sacral

The

in spinal cord

537

segments T, through L 2 (Figure

14.5).

For this reason, the sympathetic division is also referred to as the thoracolumbar division (tho"rah-kolum'bar). The presence of numerous preganglionic sympathetic neurons in the gray matter of the spinal cord produces the lateral horns the so-called visceral motor zones (see Figures 12.30b, p. 472, and

—

The

lateral horns are just posterolathorns that house somatic motor neurons. (Parasympathetic preganglionic neurons in the sacral cord are far less abundant than the comparable sympathetic neurons in the thoracolumbar regions, and lateral horns are absent in the sacral region of the spinal cord. This is a major anatomical difference between the two divisions.)

12.31, p. 473).

eral to the ventral

the esophagus.

ing fibers

The Autonomic Nervous System

Outflow and the pelvic organs outflow, which arises from

rest of the large intestine

by the sacral neurons located in the lateral gray matter of spinal cord segments S 2 -S 4 Axons of these neurons run in are served

.

the ventral roots of the spinal nerves to the ventral

rami and then branch off to form the pelvic (splanchnic) nerves (Figure 14.4), which pass through the inferior hypogastric (pelvic) plexus in the pelvic floor. Some preganglionic fibers synapse with ganglia in this plexus, but most synapse in in-

After leaving the cord via the ventral root, preganglionic sympathetic fibers pass through a white

ramus communicans

[plural,

rami communicantes

(kom-mu'ni-kan"tez)] to enter an adjoining chain (paravertebral) ganglion forming part of the sympathetic trunk or chain (Figure 14.6). Looking like strands of glistening white beads, the sympathetic trunks flank each side of the vertebral column.

Thus, these ganglia are named for their location. Although the sympathetic trunks extend from neck to pelvis, sympathetic fibers arise only from the thoracic and lumbar cord segments, as shown in Figure 14.5. The ganglia vary in size, position, and number, but typically there are 23 in each sympathetic chain 3 cervical, 1 1 thoracic, 4 lumbar, 4 sacral, and 1 coccygeal. Once a preganglionic axon reaches a chain ganglion, one of three things can happen to the axon:

—

1.

It

can synapse with a ganglionic neuron in the

same chain ganglion (pathway

Figure 14.6).

tramural ganglia in the walls of the following organs: distal half of the large intestine, urinary bladder, ureters, and reproductive organs.

to synapse in another chain ganglion (pathway (g) in

Sympathetic (Thoracolumbar) Division

these fibers running from one ganglion to another that connect the ganglia into the

2.

It

(T) in

can ascend or descend the sympathetic chain

Figure 14.6).

(It is

sympathetic trunk.

The sympathetic

division

is

more complex than the

parasympathetic division, partly because it innervates more organs. It supplies not only the visceral organs in the internal body cavities but also all visceral structures in the superficial (somatic) part of

the body. This sounds impossible, but there

planation

is

an

ex-

— some glands and smooth muscle struc-

tures in the

soma

(sweat glands and the hair-raising

muscles of the skin) require autonomic innervation and are served only by sympathetic fibers. Moreover, all arteries and veins (be they deep or superficial) have smooth muscle in their walls that is innervated by sympathetic fibers. But these matters will be explained later let us get on with the anatomy of the sympathetic division. All preganglionic fibers of the sympathetic division arise from cell bodies of preganglionic neurons arrector pili

—

can pass through the chain ganglion and emerge from the sympathetic chain without synapsin Figure 14.6). ing (pathway 3.

It

®

®

help Preganglionic fibers following pathway form the splanchnic nerves (splank'nik) that synapse with prevertebral, or collateral, ganglia located anterior to the vertebral column. Unlike chain (paravertebral) ganglia, the prevertebral ganglia are neither paired nor segmentally arranged and occur

only in the

abdomen and

pelvis.

Regardless of where the synapse occurs, all sympathetic ganglia are close to the spinal cord, and their postganglionic fibers are typically much longer than their preganglionic fibers. Recall that the opposite condition exists in the parasympathetic division, an

anatomical distinction that

is

functionally important.

538

Unit

III

Regulation and Integration of the Body

^e -

Lacrimal gland

- suprachiasmatic tides

the

II

These salts are radiopaque; hence, the pineal gland is a handy landmark for determining brain orientation in X rays. still

If

must eventually inject insulin (today manufactured by recombinant DNA techniques or produced by animals, usually pigs). Other medications that may help type diabetes are insulin resistance reducers, drugs engineered to increase

or "pineal sand").

The endocrine

like

been

not controlled,

II

absence. The Diabetes Prevention

that weight loss

oral

Orinase, which has

nies are vying to find the

mem-

branes, cells cannot take up glucose

II

diabetics also benefit

enon

membrane

a

type

from

II

II

many cases the symptoms can be managed solely by exdiabetics,

have the disease is 100%. Most type diabetics produce insulin, but for some reason the insulin receptors are unable to respond to it, a phenomwill

635

not a

major problem for type

diabetic

The Endocrine System

device that

bom-

bards skin pores with ultrasound

shock waves, enlarging them so that insulin's large molecules can be absorbed from a transdermal patch is on the threshold on the monster and looks like

Biotechnology

good bet

to win that battle soon.

nucleus of hypothalamus —> superior cervical ganglion —> pineal gland) concerning the intensity and duration of daylight. In some animals, mating behavior and gonadal size vary with changes in the relative lengths of light and dark periods, and melatonin mediates these effects. In children, melatonin may have an antigonadotropic effect, that is, it may inhibit precocious (too early) sexual maturation and thus affect the timing of puberty. The suprachiasmatic nucleus of the hypothalamus, an area referred to as our "biological clock," is richly supplied with melatonin receptors, and exposure to bright light (known to suppress melatonin secretion) can reset the clock timing. Hence, changing

636 melatonin

Unit

III

levels

Regulation and Integration of the Body

may

also be a

means by which

the

day/night cycles influence physiological processes that show rhythmic variations, such as body temperature, sleep,

and

appetite.

Structures Other hormone-producing cells occur in various organs of the body including the following (see Table 16.4):

The

atria

contain

some

,

and becomes fully activated in the kidney. form of vitamin D 3 calcitriol, is an es-

active

,

system that intestinal cells 2+ use to absorb Ca from ingested food. Without this vitamin, the bones become weak and soft. sential part of the carrier

Adipose

Adipose cells release leptin following their uptake of glucose and lipids, which they store as fat. Leptin binds to CNS neurons concerned with appetite control, producing a sensation of satiety, and appears to stimulate increased energy expenditure. Resistin, also secreted by adipose cells, is an insulin antagonist. 6.

tissue.

Developmental Aspects of the Endocrine System

Other Hormone-Producing

Heart.

liver,

The

Located deep to the sternum in the thorax is the lobulated thymus gland. Large and conspicuous in infants and children, the thymus diminishes in size throughout adulthood. By old age, it is composed largely of adipose and fibrous connective tissues. The major hormonal product of the thymic epithelial cells is a family of peptide hormones, including thymopoietins, thymic factor, and thymosins (thi'mo-sinz), which appear to be essential for the normal development of T lymphocytes and the immune response. Thymic hormones are described in Chapter 21 with the discussion of the immune system.

1.

D

molecules in epidermal cells are exposed to ultraviolet radiation. This compound then enters the blood via the dermal capillaries, is modified in terol

the

The Thymus

The

skin produces cholecalciferol, an inactive form of vitamin 3 when modified cholesSkin.

5.

specialized

Hormone-producing glands arise from all three embryonic germ layers. Endocrine glands derived from mesoderm produce steroid hormones. All others produce amines, peptides, or protein hormones.

Though not usually considered important when describing hormone effectiveness, exposure to many

cardiac muscle cells that secrete atrial natriuretic

pesticides, industrial chemicals, arsenic, dioxin,

peptide. By signaling the kidneys to increase their

other soil and water pollutants has been

production of salty urine and by inhibiting aldosterone release by the adrenal cortex, ANP reduces blood volume, blood pressure, and blood sodium concentration (see Figure 16.13).

sex hormones, thyroid hormone, and glucocorticoids have proved vulnerable to the effects of such pollutants. Interfer-

Gastrointestinal tract. Enteroendocrine cells are hormone-secreting cells sprinkled in the mucosa of the gastrointestinal (GI) tract. These scattered cells release several amine and peptide hormones that help regulate a wide variety of digestive functions, some of which are summarized in Table 16.4. Enteroendocrine cells are sometimes referred to as paraneurons because they are similar in certain ways to neurons. Many of their hormones are chemically identical to neurotransmitters, and in some cases, the hormones simply diffuse to and influence nearby target cells without first entering the bloodstream, that is, they act as local hormones or paracrines. 2.

3. Placenta. Besides sustaining the fetus during preg-

nancy, the placenta secretes several steroid and pro-

hormones that influence the course of pregnancy. hormones include estrogens and progesterone (hormones more often associated with the ovary), and human chorionic gonadotropin (hCG). tein

Placental

Kidneys. As yet unidentified cells in the kidneys secrete erythropoietin (e-rith"ro-poi'e-tin "redmaker"), a protein hormone that signals the bone marrow to increase production of red blood cells. 4.

;

disrupt endocrine function.

Thus

and

shown

to

far,

ence with glucocorticoids, which turn on many genes that may suppress cancer, may help to explain the high cancer rates in certain areas of the country. Barring exposure to environmental pollutants, and hypersecretory and hyposecretory disorders, most endocrine organs operate smoothly throughout life until old age. Aging may bring about changes in the rates of hormone secretion, breakdown, and excretion, or in the sensitivity of target cell recep-

Endocrine functioning in the elderly is difficult to research, however, because it is frequently altered by the chronic illnesses common in that age group. Structural changes in the anterior pituitary occur with age; the amount of connective tissue intors.

and the number hormone- secreting cells declines. This may or may not affect hormone production. In women, for example, blood levels and the release rhythm of ACTH remain constant, but levels of TSH and gocreases, vascularization decreases, of

GH

nadotropins increase with age. levels decline in both sexes, which partially explains muscle atrophy in old age. Endocrinologists have discovered an exciting effect of supplementation. When aging clients received injections of genetically engineered

GH

Chapter 16

TABLE 16

Selected Examples of

637

The Endocrine System

Hormones Produced by Organs Other Than the Major Endocrine Organs

Chemical Source Gl tract

Hormone

Composition

Gastrin

Peptide

Target Organ and Effects

Trigger

mucosa

Stomach

Secreted

in

response to food

Stomach: stimulates glands to release hydrochloric acid (HCI)

Stomach

Duodenum

of

Serotonin

Amine

Intestinal gastrin

Peptide

Secreted

in

response to food

Stomach: causes contraction of stomach muscle

Secreted

in

response to food,

Stomach: inhibits HCI secretion and gastrointestinal tract

especially fats

small intestine

mobility

Duodenum

Secreted

Peptide

Secretin

in

response to food

Pancreas and liver: stimulates release of bicarbonate-rich juice;

stomach:

inhibits

secretory activity

Duodenum

Cholecystokinin

Secreted

Peptide

in

response to food

Pancreas: stimulates release of

enzyme-rich juice; gallbladder: stimulates expulsion of stored bile; sphincter of Oddi: causes

(CCK)

sphincter to relax, allowing bile and pancreatic juice to enter

duodenum Kidney

Skin

(epidermal

cells)

Erythropoietin (EPO)

Glycoprotein

Erythropoietin secreted response to hypoxia

Cholecalciferol

Steroid

Cholecalciferol activated by the kidneys to active vitamin D 3 [1,25(OH) D 3 and released in response to parathyroid

(provitamin

D3

)

in

]

Bone marrow: stimulates production of red blood cells Intestine: stimulates active transport of dietary calcium

across intestinal

cell

membranes

hormone Heart

(atria)

Atrial natriuretic

Secreted

Peptide

peptide

in

response to

stretching of atria (by rising

blood pressure)

Adipose

tissue

Adipose tissue

Leptin

Resistin

Same

Peptide

GH in clinical tests over a period of 6 months, jections dramatically spurred

Secreted foods

Peptide

in

response to

as leptin

fatty

Kidney: inhibits sodium ion reabsorption and renin release; adrenal cortex: inhibits secretion of aldosterone; decreases blood pressure Brain:

suppresses appetite;

in-

creases energy expenditure Fat, muscle, liver: antagonizes insulin's action on fat, muscle, and liver cells

the in-

have been found in the release of catecholamines by

muscle growth, reduced

the adrenal medulla. The gonads, particularly the ovaries, undergo significant changes with age. In late middle age, the ovaries decrease in size and weight, and they become unresponsive to gonadotropins. As female hormone production declines dramatically, the ability to bear children ends, and problems associated with estrogen

fat, and wiped 20 years off the elders' sagging physiques. However, many questions remain concerning this therapy; for example, will supple-

body

GH

mentation also stimulate proliferation of neoplasms? The adrenal gland also shows structural changes with age, but normal controls of Cortisol appear to persist as long as a person is healthy and not stressed. Chronic stress, on the other hand, drives up blood levels of Cortisol and appears to contribute to hippocampal (and memory) deterioration. Plasma levels of aldosterone are reduced by half in old age ;

however, this may reflect a decline in renin release by the kidneys, which become less responsive to renin-evoking stimuli. No age-related differences

deficiency,

such as arteriosclerosis and osteoporosis,

begin to occur. Testosterone production by the testes also wanes with age, but this effect usually is not

seen until very old age. Glucose tolerance (the ability to dispose of a glucose load effectively) begins to deteriorate as early as the fourth decade of life. Blood glucose levels rise

higher and return to resting levels

more slowly

in the

638

Unit

Ml

Regulation and Integration of the Body

MAKING CONNECTIONS

SYSTEM CONNECTIONS Homeostatic :

Interrelationships

Between the Endocrine System and Other Body Systems

Nervous System

Many hormones (growth hormone,

thyroxine, sex

hormones) influence normal maturation and function of the nervous system

Hypothalamus controls anterior and produces two hormones

pituitary function

Cardiovascular System

hormones

influence blood volume, blood and heart contractility; erythropoietin stimulates red blood cell production Blood is the main transport medium of hormones; heart produces atrial natriuretic peptide

Several

pressure,

Lymphatic System/Immunity

Lymphocytes "programmed" by thymic hormones seed the lymph nodes; glucocorticoids depress the immune response and inflammation

Lymph provides

a route for transport of

hormones

Respiratory System

Epinephrine influences ventilation (dilates bronchioles)

Respiratory system provides oxygen; disposes of carbon dioxide; converting enzyme in lungs converts

angiotensin

I

to angiotensin

II

Digestive System Local Gl

Integumentary System

Androgens cause

influence Gl function; activated

D necessary for absorption of calcium from catecholamines influence digestive mobility

vitamin

activation of

sebaceous glands;

diet;

and secretory

estrogen increases skin hydration Skin

hormones

activity

Digestive system provides nutrients to endocrine

produces cholecalciferol (provitamin D)

organs Skeletal

System

PTH and

calcitonin regulate calcium

blood

Urinary System

growth hormone, T 3 T4 and sex hormones are necessary for normal skeletal development The skeleton provides some protection to endocrine organs, especially to those in the brain, chest, and ,

j

levels;

Aldosterone and

ADH

influence renal function;

,

erythropoietin released by kidneys influences red

blood

cell

formation

Kidneys activate vitamin

D

(considered a hormone)

pelvis

Reproductive System

Muscular System

Hypothalamic, anterior

mones

pituitary,

and gonadal hordevelopment and

direct reproductive system

Growth hormone is essential for normal muscular development; other hormones (thyroxine and catecholamines) influence muscle metabolism

function; oxytocin

Muscular system mechanically protects some endocrine glands; muscular activity elicits catecholamine release

endocrine system function

and prolactin involved in and breast-feeding Gonadal hormones feed back to influence

birth

— THE ENDOCRINE SYSTEM and

CLOSER

CONNECTIONS

Interrelationships with the Nervous

and Reproductive Systems on

normal day. The effects of trauma on

Like most body systems, the endocrine system performs many functions that benefit the body as a whole. For example, without insulin, thyroxine, and various other metabolic hormones, body cells would be unable

that's just

to get or use glucose, and would die. Likewise, total

pubertal female can result

body growth is beholden to the endocrine system, which coordinates the growth spurts with increases in skeletal and muscular mass so that we don't look out

ity; and overwhelming, prolonged emotional stress on almost anyone can lead to Addison's disease (corticosteroid burnout). The shadow the nervous system casts over the endocrine system is long indeed.

most of the time. But the interactions that are most noticeable and crucial are those that the endocrine system has with the nervous and the reproductive systems, and they begin before birth. of proportion

Nervous System

The

influence of

While

we

are

hormones on behavior

is

—

uterus, testosterone

or lack of

it

—

is

striking.

determining the

"sex" of our brain. If testosterone is produced by the exceedingly tiny male testes, then certain areas of the

numbers of androgen and thereafter determine the so-called masculine aspects of behavior (aggressiveness, etc.). Conversely, in the absence of testosterone, the brain is feminized. At puberty, Mom and Dad's "little angels," driven by raging hormones, turn into strangers. The produced first by the adrenal surge of androgens produces cortices, and then by the maturing gonads an often thoughtless aggressiveness and galloping sex brain enlarge, develop large

receptors,

—

Lack of loving care to a newborn baby results

in failure

to thrive; exceptionally vigorous athletic training

bone wasting and

in

in

the

infertil-

Reproductive System

The reproductive system mones to "order up the

is

dependent on hororgans" to match our

totally

right

genetic sex. Testosterone secretion by the testes of male embryos directs formation of the male reproduc-

the wet darkness of our mother's

in

still

a

the hypothalamic-pituitary axis can be far-reaching.

—

tive tract

and external

Without testosterone,

genitalia.

—

female structures develop

regardless of gonadal sex.

The next crucial period is puberty, when gonadal sex hormone production rises and steers maturation of the reproductive organs, bringing them to their adult structure and function. Without these hormonal signals, the reproductive organs remain childlike and the person cannot produce offspring. Pregnancy invites more endocrine system interactions with the reproductive system. The placenta, a temporary endocrine organ, churns out estrogen and progesterone, which help maintain the pregnancy and prepare the mother's breasts for lactation, as well as a

mones

number

of other hor-

bulk of hormonal activity via

and and prolactin take center stage to promote labor and delivery, and then milk production and ejection. Other than feedback inhibition exerted by its sex hormones on the hypothalamic-pituitary axis, the influence of reproductive organs on the endocrine

controls of the pituitary

system

drive, typically long

brain can rein

them

before the cognitive

organ

Not only

in its

own

is

the

in

hormonal

affairs

is

no

less

the hypothalamus an endocrine

right,

that influence maternal metabolism. During

after birth, oxytocin

in.

Neural involvement striking.

abilities of

also effectively regulates the

it

its hormonal or neural and adrenal medulla. And

is

negligible.

CLINICAL

CONNECTIONS reports that Mr.

Endocrine System

skin

Case study: We have a new patient to consider today. Mr. Gutteman, a 70-year-old male, was brought into the ER in a comatose state and has yet to come out of it. It is obvious that he suffered severe head trauma his scalp was badly lacerated, and he has an impacted skull fracture. His initial lab tests (blood and urine) were within normal limits. His fracture was repaired and the following orders (and others) were given:

Check qh

(every hour)

and record: spontaneous

behavior, level of responsiveness to stimulation,

movements, pupil size and reaction to light, speech, and vital signs. Turn patient q4h and maintain meticulous skin care and dryness.

Gutteman

is

breathing

irregularly, his

dry and flaccid, and that she has emptied his

urine reservoir several times during the day.

Upon

receiving this information, the physician ordered:

Blood and urine ketones Strict

l&O

(fluid

tests for

intake

presence of sugar and

and output recording)

is found to be losing huge amounts and the volume lost is being routinely replaced (via IV line). Mr. Gutteman's blood and urine tests are negative for sugar and ketones.

Gutteman

Mr.

of water

in

urine

Relative to these findings: 2.

What would you

lem 3.

1.

is

Is

is

it

say Mr. Gutteman's hormonal proband what do you think caused it? life

threatening? (Explain your answer.)

Explain the rationale behind these orders.

On

the second day of his hospitalization, the aide

(Answers

in

Appendix

F)

640

Unit

elderly than in

amounts

III

Regulation and Integration of the Body

young adults. The fact that near- normal by the islet

of insulin continue to be secreted

cells leads researchers to

conclude that decreasing glu-

production wanes, leaving older women vulnerable to the bone-demineralizing effects of PTH and osteoporosis.

cose tolerance with age may reflect declining receptor sensitivity to insulin (pre-type II diabetes).

Thyroid hormone synthesis and release diminish somewhat with age. Typically, the follicles are loaded with colloid in the elderly and fibrosis of the gland occurs. Basal metabolic rate declines with age. Mild hypothyroidism is only one cause of this decline. The increase in body fat relative to muscle is equally important, because muscle tissue is more active metabolically than fat. The parathyroid glands change little with age, and PTH levels remain fairly normal throughout life.

Estrogens protect

izing effects of

women against

PTH, but

after

the demineral-

menopause estrogen

*

*

*

we have covered the general hormone action and have provided

In this chapter,

mechanisms an overview

of

of the major endocrine organs, their and their most important physiological effects, as summarized in Making Connections on p. 638. However, every one of the hormones discussed here comes up in at least one other chapter, where its actions are described as part of the functional framework of a particular organ system. For example, the effects of PTH and calcitonin on bone mineralization are described in Chapter 6 along with the discussion of bone remodeling.

chief targets,

Related Clinical Terms Hirsutism (her'soot-izni; hirsut = hairy, rough) Excessive hair growth; usually refers to this phenomenon in women and reflects excessive androgen production.

hormone and thus

Hypophysectomy

Thyroid storm (thyroid

(hi-pof'i-sek'to-me) Surgical removal of

the pituitary gland.

Prolactinoma (pro-lak"ti-no'mah oma = tumor) The most type (30-40% or more) of pituitary gland tumor; evidenced by hypersecretion of prolactin and menstrual dis;

common

turbances in

women.

hypothalamic release of growth hormone-releasing anterior pituitary secretion of growth

hormone. crisis)

A

sudden and dangerous

increase in all of the symptoms of hyperthyroidism due to excessive amounts of circulating TH. Symptoms of this hypermetabolic state include fever, rapid heart rate, high blood pressure, dehydration, nervousness, and tremors. Precipitating factors include stressful situations, excessive intake of supplements, and trauma to the thyroid gland.

TH

Psychosocial dwarfism Dwarfism (and failure to thrive) resulting from stress and emotional disorders that suppress

Chapter Summary Media study

tools that could provide

you additional help

in

reviewi ng sp ecific key topics of Chapter 16 are referenced

below.

M\M

= Interactive Physiology

The nervous and endocrine systems are the major controlling systems of the body. The nervous system exerts 1.

Hormones

2.

mediated by hormones and are more prolonged.

Hormonally regulated processes include reproduction;

MLM

The Endocrine System: An Overview

(pp.

604-605)

605-609)

by stimulating or inhibiting

hormone stimulation may

involve

changes in membrane permeability; enzyme synthesis, activation, or inhibition; secretory activity; gene activation; and 4. Second-messenger mechanisms employing intracellular messengers and transduced by G proteins are a common means by which amino acid-based hormones interact with

AMP

are the pituitary, thyroid,

thymus glands, as well as the pancreas and gonads. The hypothalamus is a neuroen-

their target cells. In the cyclic system, the hormone binds to a plasma membrane receptor that couples to a G protein. When the protein is activated it, in turn, couples to adenylate cyclase, which catalyzes the synthesis of cyclic from ATP. Cyclic initiates reactions that activate protein kinases and other enzymes, leading to cellular response. The PIP-calcium signal mechanism, involving phosphatidyl inositol, is another important second-messenger system. Other presumed "messengers" are cyclic and calcium.

G

AMP

docrine organ. 3. Local hormones are not generally considered part of the endocrine system. They include autocrines, which act on

M1M

alter cell activity

(pp.

mitosis.

parathyroid, adrenal, pineal, and

the cells that secrete them, and paracrines, which act different cell type nearby.

Hormones

Hormone Action

3. Cell responses to

Endocrine organs are ductless, well-vascularized glands that release hormones directly into the blood or lymph. They are small and widely separated in the body.

The major endocrine organs

of

characteristic cellular processes of their target cells.

1.

2.

acid based.

Endocrine System; Topic: Biochemistry, Secretion, and Transport of Hormones, page 3.

Mechanisms 2.

growth and development; mobilization of body defenses; maintaining electrolyte, water, and nutrient balance,- and regulating cellular metabolism and energy balance.

605-611)

The Chemistry of Hormones (p. 605) 1. Most hormones are steroids or amino

rapid controls via nerve impulses; the endocrine system's effects are

(pp.

on

Endocrine System; Topic: Endocrine System Review, page 3.

a

AMP

GMP

WIM

Endocrine System; Topic: The Actions of Hormones on Target Cells, pages 3-7.

The Endocrine System

Chapter 16

hormones (and thyroid hormone) enter their and effect responses by activating DNA, which messenger RNA formation leading to protein

Steroid

5.

target cells initiates

synthesis. (p.

ability of a target cell to

Hormone receptors are dynamic structures. Changes in number and sensitivity of hormone receptors may occur in 7.

response to high or low levels of stimulating hormones.

BU Endocrine System; Topic: The Actions of Hormones on Target Cells, page 3. Half-Life, Onset,

and Duration of Hormone Activity

609-610)

(pp.

Blood levels of hormones

balance between seliver and kidneys are the major organs that degrade hormones; breakdown products are excreted in urine and feces. 8.

reflect a

cretion and degradation/excretion.

Hormone

The

and duration of and vary from hormone to hormone. 9.

half-life

Hormones

Interaction of

10. Permissiveness cannot exert its full

is

activity are limited

at Target Cells

(p.

610)

the situation in which a hormone without the presence of another

effects

the

Synergism occurs

same

when two

effects in a target cell

more hormones produce

or

and

their results are amplified.

Antagonism occurs when a hormone opposes or reverses the effect of another hormone. 12.

Control of

Hormone

Release

(pp.

hormones

by humoral, neural, or hormonal stimuli. Negative feedback is important in regulating hormone levels in the blood.

The nervous

14.

system, acting through hypothalamic concan in certain cases override or modulate hormonal

effects.

—

7. The gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) regulate the functions of the gonads in both sexes. FSH stimulates sex cell production; LH stimulates gonadal hormone production. Gonadotropin levels rise in response to gonadotropinreleasing hormone (GnRH). Negative feedback of gonadal hormones inhibits gonadotropin release.

8. Prolactin

—

(PRL) promotes milk production in humans.

prompted by prolactin-releasing hormone (PRH) and inhibited by prolactin-inhibiting hormone (PIH).

Its

secretion

is

9. The neurohypophysis stores and releases two hypothalamic hormones, oxytocin and antidiuretic hormone (ADH).

10. Oxytocin stimulates powerful uterine contractions,

which

trigger labor

and delivery

women.

It

of

an

and milk ejecpromote sexual mediated reflexively by infant,

also appears to

arousal and nurturing. Its release is the hypothalamus and represents a positive feedback

mechanism. 11. Antidiuretic hormone stimulates the kidney tubules to reabsorb and conserve water; as urine output declines, blood volume and blood pressure rise. is released in response to high solute concentrations in the blood and inhibited by low solute concentrations in the blood. Hyposecretion results in diabetes insipidus.

The Thyroid Gland (pp. 618-623) 12. The thyroid gland is located in the

anterior throat. Thy-

roid follicles store thyroglobulin, a colloid

Endocrine System; Topic: The Hypothalamic-Pituitary Axis, pages 4 and 5.

M1M

ACTH

ADH

610-11)

13. Endocrine organs are activated to release their

trols,

6. Adrenocorticotropic hormone (ACTH) stimulates the adrenal cortex to release corticosteroids. release is triggered by corticotropin-releasing hormone (CRH) and inhibited by rising glucocorticoid levels.

tion in nursing

hormone. 11.

Thyroid-stimulating hormone (TSH) promotes normal activity of the thyroid gland. Thyrotropinreleasing hormone (TRH) stimulates its release; negative feedback of thyroid hormone inhibits it.

development and

609)

respond to a hormone depends on the presence of receptors, within the cell or on its plasma membrane, to which the hormone can bind.

The

hormone (GHIH), or somatostatin. Hypersecretion causes gigantism in children and acromegaly in adults; hyposecrction in children causes pituitary dwarfism. 5.

Target Cell Specificity 6.

641

roid

hormone

is

from which thy-

derived.

13. Thyroid hormone (TH) includes thyroxine (T 4 and triiodothyronine (T,,), which increase the rate of cellular metabolism. Consequently, oxygen use and heat production )

Major Endocrine Organs

The

Pituitary

(pp. 61

Gland (Hypophysis)

1

-636)

(pp.

611-618)

rise.

1.

The

pituitary gland hangs

and

from the base

of the brain by

enclosed by bone. It consists of a hormoneproducing glandular portion (anterior pituitary) and a neural portion (posterior pituitary), which is an extension of the a stalk

is

The hypothalamus

hormonal output of and inhibiting hormones

regulates the

Four of the six adenohypophyseal hormones are tropic hormones that regulate the function of other endocrine or3.

Most anterior pituitary hormones exhibit a diurnal rhythm of release, which is subject to modification by stim-

gans.

influencing the hypothalamus.

4. Growth hormone (GH) is an anabolic hormone that stimulates growth of all body tissues but especially skeletal muscle and bone. It may act directly or indirectly via insulin-like growth factors (IGFs). mobilizes fats, stimulates protein synthesis, and inhibits glucose uptake and metabolism. Secretion is regulated by growth hormone-re-

15. Most T 4 is converted to T 3 (the more active form) in the target tissues. These hormones appear to act via a steroidlike

hormone (GHRH) and growth hormone-inhibiting

mechanism.

16. Hypersecretion of thyroid hormone results most importantly in Graves' disease; hyposecretion causes cretinism in

infants

and myxedema

in adults.

by the parafollicular (C) cells of the thyroid gland in response to rising blood calcium levels, depresses blood calcium levels by inhibiting bone matrix resorption and enhancing calcium deposit in bone. 17. Calcitonin, produced

miM

GH

leasing

hormones from the colloid for release. Rising hormone feed back to inhibit the pituitary

and hypothalamus. (a)

the anterior pituitary via releasing and (b) synthesizes two hormones that it exports to the posterior pituitary for storage and later release.

uli

splitting of the

levels of thyroid

hypothalamus. 2.

14. Secretion of thyroid hormone, prompted by TSH, requires reuptake of the stored colloid by tbe follicle cells and

Endocrine System; Topic: The Hypothalamic-Pituitary Axis, page

The

6.

Parathyroid Glands

(pp.

623-624)

18. The parathyroid glands, located on the dorsal aspect of the thyroid gland, secrete parathyroid hormone (PTH),

642

Unit

Regulation and Integration of the Body

III

which causes an increase in blood calcium levels by targeting bone, the intestine, and the kidneys. PTH is the antagonist of calcitonin.

19.

PTH

and

is

release

is

by

triggered

falling

blood calcium levels

glucose uptake and metabolism by most body cells. Hyposecretion of insulin results in diabetes mellitus cardinal signs are polyuria, polydipsia, and polyphagia. ;

BM Endocrine System; Topic: The Actions of Hormones on Target Cells, pages 5 and

inhibited by rising blood calcium levels.

20. Hyperparathyroidism results in hypercalcemia and

and

its effects

in

roidism leads to

all

extreme bone wasting. Hypoparathyhypocalcemia, evidenced by tetany and

respiratory paralysis.

The Adrenal (Suprarenal) Glands 21. The paired adrenal (suprarenal)

(pp.

624-630)

glands

sit

atop the kid-

neys. Each adrenal gland has two functional portions, the

cortex and the medulla. 22. Three groups of steroid cortex from cholesterol.

hormones

are produced by the

6.

The Gonads (pp. 633-634) 31. The ovaries of the female, located release two main hormones. Secretion

in the pelvic cavity,

of estrogens by the ovarian follicles begins at puberty under the influence of FSH. Estrogens stimulate maturation of the female reproductive system and development of the secondary sex characteristics. Progesterone is released in response to high blood levels of LH. It works with estrogens in establishing the menstrual cycle.

regulate levels of other electrolytes that are coupled to

32. The testes of the male begin to produce testosterone at puberty in response to LH (ICSH). Testosterone promotes maturation of the male reproductive organs, development of secondary sex characteristics, and production of sperm by the testes.

sodium transport. Release of aldosterone is stimulated by the renin-angiotensin mechanism, rising potassium ion or falling sodium levels in the blood, and ACTH. Atrial natriuretic peptide inhibits aldosterone release.

The Pineal Gland (pp. 634-636) 33. The pineal gland is located in the diencephalon. Its primary hormone is melatonin, which influences daily rhythms

23. Mineralocorticoids (primarily aldosterone) regulate

sodium ion reabsorption by the kidneys and thus

indirectly

24. Glucocorticoids (primarily Cortisol) are important metabolic hormones that help the body resist stressors by increasing blood glucose, fatty acid and amino acid levels, and blood pressure. High levels of glucocorticoids depress the immune system and the inflammatory response. is the major stimulus for glucocorticoid release.

ACTH

25. Gonadocorticoids (mainly androgens) are produced in small amounts throughout life. 26. Hypoactivity of the adrenal cortex results in Addison's can result in aldosteronism, Cush-

disease. Hypersecretion ing's disease,

and androgenital syndrome.

27. The adrenal medulla produces catecholamines (epinephrine and norepinephrine) in response to sympathetic nervous system stimulation. Its catecholamines enhance and prolong the fight-or-flight response to short-term stressors. Hypersecretion leads to symptoms typical of sympathetic nervous system overactivity.

BIM

Endocrine System; Topic: Response to

The Pancreas (pp. 630-633) 28. The pancreas, located in the abdomen

Stress,

pages 5-8.

close to the

stomach, is both an exocrine and an endocrine gland. The endocrine portion (pancreatic islets) releases insulin and glucagon and smaller amounts of other hormones to the blood.

29. Glucagon, released by alpha (a) cells when blood levels of glucose are low, stimulates the liver to release glucose to the blood.

30. Insulin is released by beta (fj) cells when blood levels of glucose (and amino acids) are rising. It increases the rate of

and

may

have an antigonadotropic

effect in

humans.

The Thymus (p. 636) 34. The thymus gland,

located in the upper thorax, declines and function with age. Its hormones, thymosins, thymic factor, and thymopoietins, are important to the normal development of the immune response. in size

Other Hormone-Producing Structures (p.

636)

1 Many body organs not normally considered endocrine gans contain isolated cell clusters that secrete hormones. .

Examples include the heart

or-

(atrial natriuretic peptide); gas-

and others); the placenta (hormones of pregnancy estrogen, progesterone, and others); the kidneys (erythropoietin); skin (cholecalciferol); and adipose tissue (leptin and resistin). trointestinal tract organs (gastrin, secretin,

—

Developmental Aspects of the Endocrine System (pp. 636-637, 640) 1. Endocrine glands derive from all three germ layers. Those derived from mesoderm produce steroidal hormones; the others produce the amino acid-hased hormones.

2. The natural decrease in function of the female's ovaries during late middle age results in menopause.

3. The efficiency of all endocrine glands seems to decrease gradually as aging occurs. This leads to a generalized increase in the incidence of diabetes mellitus and a lower

metabolic

rate.

Review Questions Multiple Choice/Matching

3.

(Some questions have more than one correct answer. Select the best answer or answers from the choices given.) 1.

The major stimulus

is (a)

2.

hormonal,

The

(b)

for release of parathyroid

humoral,

(c)

anterior pituitary secretes

hormone,

(b)

growth hormone,

hormone

neural.

(c)

all but (a) antidiuretic gonadotropins, (d) TSH.

A hormone nor involved

glucagon,

(b)

cortisone,

(c)

in sugar

metabolism

aldosterone,

(d)

is (a)

insulin.

4. Parathyroid hormone (a) increases bone formation and lowers blood calcium levels, (b) increases calcium excretion from the body, (c) decreases calcium absorption from the gut, (d) demineralizes bone and raises blood calcium levels. 5.

Choose from the following key

described.

to identify the

hormones

Chapter 16

Key:

(a)

aldosterone

hormone growth hormone luteinizing hormone

(b) antidiuretic (c)

(d) (

1

)

(2)

(3) (4)

prolactin

(g)

(h)

T 4 and T3 TSH

19.

uterine contractions during birth

hormone

that stimulates the thyroid gland

hormone

to secrete thyroid (9) a

hormone

The

anterior pituitary

endocrine organ, but

it,

is

often referred to as the master

has a "master."

too,

What

secreted by the neurohypophysis (two

controls

the release of anterior pituitary hormones? 20.

The

posterior pituitary

is

Why not? What is it? 21. A colloidal, or endemic,

not really an endocrine gland.

goiter

malfunction of the thyroid gland.

is

not really the result of

What does cause

result

23.

as a

Name

mones 24.

it?

some problems that elderly people might have of decreasing hormone production.

22. List

major metabolic hormone(s) of the body causes reabsorption of sodium ions by the kidneys

(8) tropic

643

18. Name two endocrine glands (or regions) that are important in the stress response, and explain why they are important.

hormones

(5) increases

(7)

oxytocin

(f)

important anabolic hormone; many of its effects mediated by IGFs involved in water balance; causes the kidneys to conserve water stimulates milk production tropic hormone that stimulates the gonads to secrete sex

(6)

(e)

The Endocrine System

a hormone secreted by a muscle cell and two horsecreted by neurons.

How are

the hyperglycemia and lipidemia of insulin de-

ficiency linked?

possible choices)

hormone

(10) the only steroid

A hypodermic

6.

in the

list

would

injection of epinephrine

(a)

Critical

in-

crease heart rate, increase blood pressure, dilate the bronchi of the lungs, and increase peristalsis, (b) decrease heart rate,

decrease blood pressure, constrict the bronchi, and increase peristalsis, (c) decrease heart rate, increase blood pressure, constrict the bronchi, and decrease peristalsis, (d) increase heart rate, increase blood pressure, dilate the bronchi, and decrease peristalsis. 7. Testosterone is to the male as what hormone female? (a) luteinizing hormone, (b) progesterone,

gen,

(d)

is

to the

(c)

estro-

prolactin.

8. If anterior pituitary secretion is deficient in a

child, the child will

dwarf but have

(a)

fairly

sexually at an earlier

develop acromegaly,

(b)

growing

become

a

normal body proportions, (c) mature than normal age, (d) be in constant

danger of becoming dehydrated.

adequate carbohydrate intake, secretion of insulin results in (a) lower blood sugar levels, (b) increased cell 9. If there is

utilization of glucose,

Hormones

10.

(a)

storage of glycogen,

(c)

of these.

(d) all

are produced by exocrine glands,

body in blood,

carried to all parts of the

constant concentration in the blood,

hormone producing

(c)

remain

(d) affect

(b)

are

at

only non-

organs.

Some hormones

by

increasing the synthesis of enconverting an inactive enzyme into an active en ;

11.

act

(a)

zymes, (b) zyme, (c) affecting only specific target organs,

(d) all

of these!

Absence of thyroxine would result in (a) increased heart and increased force of heart contraction, (b) depression the CNS and lethargy, (c) exophthalmos, (d) high meta-

12.

rate of

bolic rate.

(b)

cells are

found in the

anterior pituitary gland,

14. Atrial natriuretic

(c)

(a) parathyroid gland, adrenal gland, (d) pineal gland.

hormone

secreted by the heart has ex-

actly the opposite function of this

hormone

zona glomerulosa:

hormone,

(c)

Questions Richard Neis had symptoms of excessive secretion of (high blood calcium levels), and his physicians were certain he had a parathyroid gland tumor. Yet when surgery was performed on his neck, the surgeon could not find the parathyroid glands at all. Where should the surgeon look next to find the tumorous parathyroid gland? 1

calcitonin,

2. Mary Morgan has just been brought into the emergency room of City General Hospital. She is perspiring profusely and is breathing rapidly and irregularly. Her breath smells

acetone (sweet and fruity), and her blood sugar tests out 650 mg/100 ml blood. She is in acidosis. What hormone drug should be administered, and why? like

at

been growing by leaps and bounds,- his height is 100% above normal for his age. He has been complaining of headaches and vision problems. A

3. Johnny, a five-year-old boy, has

CT scan

Which

being secreted in excess?

(b)

(a)

(d)

(a)

antidiuretic

aldosterone,

(e)

secreted by the (b)

epinephrine,

androgens.

hormone. type of

— plasma membrane — would be expected

hormone

bound or intracellular most long-lived response

receptor

to provide the

to

hormone binding and why?

(a) Describe the body location of each of the following endocrine organs: anterior pituitary, pineal gland, pancreas,

17.

ovaries, testes,

and adrenal glands,

produced by each organ.

(b)

List the

hormones

What hormone

What

4. As Martina sat lazily scanning the newspaper, a headline caught her eye, "Anabolic steroids declared a controlled subit's about stance." Hmm, she thought, that's interesting time those drugs got put in the same class with heroin. That night, she awoke from a dream in a cold sweat. In her dream all her male friends were being rounded up by government drug agents and charged with illegal possession of a con.

What is the connection, the headline and Martina's bizarre dream?

if

.

any,

.

between

5. Roger Proulx has severe arthritis and has been taking prednisone (a glucocorticoid) at pharmacological levels for two months. He isn't feeling well, complains of repeated "colds," and is extremely "puffy" (edematous). Explain the reason for these symptoms.

_

16.

reveals a large pituitary tumor,

condition will Johnny exhibit if corrective measures are not taken? (c) What is the probable cause of his headaches and visual problems? is

Short Answer Essay Questions 15. Define

.

PTH

trolled substance.

Chromaffin

13.

Thinking and

Clinical Application

MvA&P

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Blood

Overview: Blood Composition and Functions (pp. 645-646) 1.

Describe the composition and

9. •

Describe the process of hemostasis. List factors that

and

physical characteristics of

limit clot formation

whole blood. Explain why

prevent undesirable clotting.

it is

classified as a connective

2.

Hemostasis (pp. 661-667)

10. Give examples of hemostatic

tissue.

disorders. Indicate the cause of

List six functions of blood.

each condition.

Blood Plasma (pp. 646-647) 3. Discuss the composition and functions of plasma.

Transfusion and Blood

Replacement

(pp.

11. Describe the

667-670)

ABO

and Rh

blood groups. Explain the basis

Formed Elements 4.

(pp.

647-661)

Describe the structure, function,

of transfusion reactions.

12. Describe the function of blood

and production

of

expanders and the circumstances for their use.

erythrocytes. 5.

6.

Describe the chemical

makeup

of hemoglobin.

Diagnostic Blood Tests

List the classes, structural

13. Explain the diagnostic

characteristics,

importance of blood

and functions

(p.

671)

testing.

of leukocytes. Also describe

leukocyte genesis. 7.

Describe the structure and function of platelets.

8.

Give examples of disorders caused by abnormalities of each of the formed elements. Explain the mechanism of each disorder.

Developmental Aspects of Blood (p. 671) 14. Describe changes in the sites of

blood production and in the type of hemoglobin produced after birth.

15.

Name some blood that

with

disorders

become more common age.

Chapter 17

the river of life that surges within us, transporting nearly everything that must be carried from one place to another. Long before

Blood

is

modern medicine, blood was viewed

as magical

—

— an

because elixir that held the mystical force of life when it drained from the body, life departed as well. Today centuries later, blood still has enormous importance in the practice of medicine. Clinicians

examine

it

more often than any other

tissue

when

trying to determine the cause of disease in their patients.

In this chapter,

we

describe the composition and

Overview: Blood Composition and Functions

Components Blood is the only fluid tissue in the body. Although blood appears to be a thick, homogeneous liquid, the microscope reveals that it has both cellular and liquid components. Blood is a specialized type of connective tissue in which living blood cells, the formed elements, are suspended in a nonliving fluid matrix called

plasma (plaz'mah). The collagen and

fibers typical of other

transport "vehicle" for the organs of the cardiovascular system. To get started, we need a brief

visible as fibrin strands during blood clotting.

overview of blood circulation, which is initiated by the pumping action of the heart. Blood exits the

heavier formed elements are packed

and enter the body tissues, and carbon dioxide and wastes move from the tissues to the bloodstream.

As oxygen- deficient blood leaves the capillary beds, it flows into veins, which return it to the heart. The returning blood then flows from the heart to the lungs, where it picks up oxygen and then returns to the heart to be pumped throughout the body once again. Now let us look more closely at the nature of blood.

^

FIGURE is

the

If

a

sample of blood

trifugal force

and the

it

a

blood sample

separates into layers, the heaviest particles (erythrocytes) moving to test tube.

The

least

dense component

is

is

less

spun

in a centrifuge, the

down by

cen-

dense plasma remains at

the top (Figure 17.1). Most of the reddish mass at the bottom of the tube is erythrocytes (e-rith'ro-sits; erythro = red), the red blood cells that transport oxygen. A thin, whitish layer called the huffy coat is present at the erythrocyte-plasma junction. This layer contains leukocytes [leuko = white), the white blood cells that act in various ways to protect the body, and platelets, cell fragments that help stop bleeding. Erythrocytes normally constitute about 45% of the total volume of a blood sample, a percentage known as the hematocrit (he-mat'o-krit;

The major components of whole blood. When

17.1

bottom of the

layer.

from blood, but dissolved fibrous proteins become

Which of the percentages given in this figure represents the measurement called the hematocrit?

centrifuged,

elastic

connective tissues are absent

functions of this life-sustaining fluid that serves as a

heart via arteries, which branch repeatedly until they become tiny capillaries. By diffusing across the capillary walls, oxygen and nutrients leave the blood

645

Blood

plasma, which

is

the top

646

Maintenance of the Body

Unit IV

"blood fraction"). Normal hematocrit values vary. In healthy males the norm is 47% ± 5%; in females it is 42% ± 5%. Leukocytes and platelets contribute less than 1% of blood volume. Plasma makes up most of the remaining 55% of whole blood.

Physical Characteristics

blood proteins act to prevent excessive fluid loss from the bloodstream into the tissue spaces. As a result, the fluid volume in the blood vessels remains ample to support efficient blood circulation to all parts of the body.

Protection

and Volume

Protective functions of blood include:

Blood

is

a sticky opaque fluid with a characteristic

metallic taste.

the

first

time

As

we

children,

we

discover

its

Preventing blood

saltiness

stick a cut finger into our

mouth.

Depending on the amount of oxygen it is carrying, the color of blood varies from scarlet (oxygen-rich) to dark red (oxygen-poor). Blood is more dense than water and about five times more viscous, largely because of its formed elements. Blood is slightly alkaline, with a pH between 7.35 and 7.45, and its temperature (38°C or 100.4°F) is always slightly higher than body temperature. Blood accounts for approximately 8% of body weight. Its average volume in healthy adult males is 5-6 L (about 1.5 gallons), somewhat greater than in healthy adult females (4-5 L).

aged, platelets

loss.

When a blood vessel is dam-

and plasma proteins

mation, halting blood

initiate clot for-

loss.

Preventing infection. Drifting along in blood are complement proteins, and white blood cells, all of which help defend the body against foreign invaders such as bacteria and viruses. antibodies,

,

Blood Plasma Blood plasma is a straw-colored, sticky fluid (see Figure 17.1). Although it is mostly water (about 90%), plasma contains over 100 different dissolved solutes, including nutrients, gases, hormones, wastes and cell activity, ions, and proteins. Table 17.1 summarizes the major plasma components. Plasma proteins, accounting for about 8% by weight of plasma volume, are the most abundant plasma solutes. Except for hormones and gamma globulins, most plasma proteins are produced by the liver. Plasma proteins serve a variety of functions, but they are not taken up by cells to be used as fuels or metabolic nutrients as are most other plasma solutes, such as glucose, fatty acids, and oxygen.

products of

Functions Blood performs a number of functions, all concerned way or another with substance distribution, regulating blood levels of particular substances, or

in one

body protection. Distribution Distribution functions of blood include:

Delivering oxygen from the lungs and nutrients

from the digestive

tract to all

body

cells.

Transporting metabolic waste products from

cells

to elimination sites (to the lungs for elimination of

carbon dioxide, and to the kidneys for disposal of trogenous wastes in urine).

ni-

Transporting hormones from the endocrine organs to their target organs.

Albumin

(al-bu'min) accounts for

some 60%

of

plasma protein. It acts as a carrier to shuttle certain molecules through the circulation, is an important blood buffer, and is the major blood protein contributing to the plasma osmotic pressure (the pressure that helps to keep water in the bloodstream). (Sodium ions are the other major solute contributing to blood

osmotic pressure.)

The makeup

of plasma varies continuously as remove or add substances to the blood. However, assuming a healthy diet, plasma composition is kept relatively constant by various homeostatic mechanisms. For example, when blood protein levels drop undesirably, the liver makes more proteins; and when the blood starts to become too acidic (acidosis), both the respiratory system and the kidneys cells

Regulation Regulatory functions of blood include:

Maintaining appropriate body temperature by absorbing and distributing heat throughout the body and to the skin surface to encourage heat loss.

Maintaining normal pH in body tissues. Many blood proteins and other bloodborne solutes act as buffers to prevent excessive or abrupt changes in blood pH that could jeopardize normal cell activities. Additionally blood acts as the reservoir for the body's "alkaline reserve" of bicarbonate atoms.

Maintaining adequate

fluid

volume

in the circula-

tory system. Salts (sodium chloride and others) and

are called into action to restore plasma's normal,

pH. Body organs make dozens of adjustments, day in and day out, to maintain the many plasma solutes at life-sustaining levels. In addition to transporting various solutes around the body, plasma distributes heat (a by-product of cellular metabolism) throughout the body. slightly alkaline

Chapter 17

TABLE

17. 1

^

r Platelets

Composition of Plasma

Constituent

Description and Importance

Water

90%

Erythrocytes

647

Blood

Monocyte

-

of plasma volume; dissolving and suspending medium for solutes of blood; absorbs heat

Solutes

8%

Proteins

Albumin

(by weight) of

plasma volume

60%

of plasma proteins; produced by liver; exerts osmotic pressure to maintain water

balance between blood and tissues Globulins alpha, beta

36%

of

plasma proteins

Produced by bind to

transport proteins that metal ions, and fat-soluble

liver;

lipids,

vitamins

gamma

Antibodies released primarily by plasma cells during immune response

Clotting

4%

proteins

and prothrombin produced by blood clotting

Neutrophils-1 liver;

act

(such as complement),

Nonprotein nitrogenous substances

By-products of cellular metabolism, such as urea, uric acid, creatinine,

and ammonium

salts

and

Nutrients

Materials absorbed from digestive tract

transported for use throughout body; include glucose and other simple carbohydrates, amino acids (digestion products of proteins), fatty acids, glycerol

and triglycerides and vitamins

gases

Cations include sodium, potassium, calcium, magnesium; anions include chloride, phosphate, sulfate, and bicarbonate; help to maintain plasma osmotic pressure and normal blood pH

Oxygen and carbon dioxide; some dissolved oxygen (most bound to hemoglobin inside RBCs); carbon dioxide transported bound to hemoglobin in RBCs and as bicarbonate ion dissolved

in

plasma

Formed Elements The formed elements

of blood, erythrocytes, leuko-

have some unusual features. not even true cells: Erythrocytes have no nuclei or organelles, and platelets are cell fragments. Only leukocytes are complete cells. (2) Most of the formed elements survive in the bloodstream for only a few days. (3) Most blood cells do not divide. Instead, they are continuously renewed by division of cells in bone marrow, where

cytes, (1)

and

Two

platelets,

of the three are

they originate. If

you examine a stained smear of human blood light microscope, you will see disc-shaped

under the

red blood

cells,

a variety of gaudily stained spherical

white blood cells, and some scattered platelets that look like debris (Figure 17.2). Erythrocytes vastly outnumber the other types of formed elements. Table 17.2 on p. 656 summarizes the important characteristics of the

formed elements.

(fat

products), cholesterol,

Respiratory

FIGURE 17.2 Photomicrograph of a human blood smear stained with Wright's stain.

hormones

(organic)

Electrolytes

Lymphocyte

in

Metabolic enzymes, antibacterial proteins

Others

L-

of plasma proteins; include fibrinogen

Erythrocytes Structural Characteristics Erythrocytes or red blood cells (RBCs) are small cells, about 7.5 |xm in diameter. Shaped like biconflattened discs with depressed centers cave discs (Figure 17.3) their thin centers appear lighter in color than their edges. Consequently, erythrocytes look like miniature doughnuts when viewed with a microscope. Mature erythrocytes are bound by a plasma membrane, but lack a nucleus (are anucleate) and have essentially no organelles. In fact, they are little more than "bags" of hemoglobin (Hb), the RBC protein that functions in gas transport. Other proteins are present such as antioxidant enzymes that rid the body of harmful oxygen radicals, but most function mainly to maintain the plasma membrane or promote changes in RBC shape. For example, the biconcave shape of an erythrocyte is main-

—

—

tained by a network of proteins, especially one called spectrin, attached to the cytoplasmic face of its plasma membrane. Because the spectrin net is de-

formable, it gives erythrocytes flexibility to change shape as necessary to twist, turn, and become cupshaped as they are carried passively through capillar-

—

with diameters smaller than themselves then to resume their biconcave shape.

ies

— and

648

Unit IV

Maintenance of the Body

Function Erythrocytes are completely dedicated to their job of respiratory gas (oxygen and carbon dioxide) trans-2.0

urn

Hemoglobin, the protein that makes red blood cells red, binds easily and reversibly with oxygen, and most oxygen carried in blood is bound to hemoglobin. Normal values for hemoglobin are 14-20 grams port.

per 100 milliliters of blood (g/100 ml) in infants, 13-18g/100mlin adult males, and 12-16 g/100 ml in adult females.

-7.5

urn

17.3

A

single red blood cell contains about

250 million hemoglobin molecules, so each of these tiny cells can scoop up about 1 billion molecules of

Structure of erythrocytes. Cut side

view above; a superficial surface view below. Notice the distinctive

—

—

of oxygen.

Top view

FIGURE

Hemoglobin is made up of the protein globin bound to the red heme pigment. Globin consists of four polypeptide chains two alpha (a) and two beta each bound to a ringlike heme group. Each (P) heme group bears an atom of iron set like a jewel in its center (Figure 17.4). Since each iron atom can combine reversibly with one molecule of oxygen, a hemoglobin molecule can transport four molecules

biconcave shape.

oxygen!

The

fact

that

hemoglobin

is

contained in

erythrocytes, rather than existing free in plasma, it from breaking into fragments (1) would leak out of the bloodstream (through the rather porous capillary membranes) and (2) from contributing to blood viscosity and osmotic

prevents that

The

erythrocyte is a superb example of complementarity of structure and function. It picks up oxygen in the capillary beds of the lungs and releases it to tissue cells across other capillaries throughout the body. It also transports some 20% of the carbon dioxide released by tissue cells back to the lungs. Each erythrocyte structural characteristic contributes to its gas transport functions: (1) Its small size and biconcave shape provide a huge surface area relative to volume (about 30% more surface area than comparable spherical cells). Because no point within its cytoplasm is far from the surface, the biconcave disc shape is ideally suited for gas exchange. (2) Discounting water content, an erythrocyte is over 97% hemoglobin, the molecule that binds to and transports respiratory gases. (3) Because erythrocytes lack mitochondria and generate ATP by anaerobic mechanisms, they do not consume any of the oxygen they are transporting,

making them very

efficient

oxygen trans-

porters indeed.

Erythrocytes are the major factor contributing to blood viscosity. Women typically have a lower red blood cell count than men (4.3-5.2 million cells per cubic millimeter of blood versus 5.1-5.8 million cells per cubic millimeter respectively). When the number of red blood cells increases beyond the normal range, blood viscosity rises and blood flows

more

slowly. Similarly, as the number of red blood drops below the lower end of the range, the blood thins and flows more rapidly. cells

pressure.

Oxygen loading occurs direction of transport

is

in the lungs

from lungs

and the

to tissue cells.

As oxygen-deficient blood moves through

the lungs, oxygen diffuses from the air sacs of the lungs into the blood and then into the erythro-

cytes, where it binds to hemoglobin. When oxygen binds to iron, the hemoglobin, now called oxyhemoglobin, assumes a new three-dimensional shape and becomes ruby red. In the tissues, the process is reversed. Oxygen detaches from iron, hemoglobin resumes its former shape, and the resulting deoxyhemoglobin, or reduced hemoglobin, becomes dark red. The released oxygen diffuses from the blood into the tissue fluid and then into the tissue cells. About 20% of the carbon dioxide transported in the blood combines with hemoglobin, but it binds to globin's amino acids rather than with the heme group. This formation of carbaminohemoglobin (kar-bam"i-no-he"mo-glo'bin) occurs more readily when hemoglobin is in the reduced state (dissociated from oxygen). Carbon dioxide loading occurs in

the tissues and the direction of transport is from tissues to lungs, where carbon dioxide is eliminated from the body. The mechanisms of loading and unloading these respiratory gases are described in

Chapter 22.

Chapter 17

How many

9

molecules of oxygen can

649

Blood

hemoglobin

a

molecule transport?

H 3C

CH 2 CH 2 COOH

H 2 C=CH

HoC

H2C=CH

CH3

Polypeptide chain

(a)

(b) Iron-containing

Hemoglobin

FIGURE

1

7.4

protein globin

Structure of hemoglobin,

bound

to the iron-containing

(a)

Hemoglobin

heme

is

at

its

is

complexed

with a

center, (b) Structure

heme group, shown of a heme group.

of the

pigments. Each globin molecule

has four polypeptide chains: two alpha (a) chains and two beta chain

composed

heme group

((3)

chains. Each

as a circular green structure with iron

Although the various formed elements have

dif-

hematopoiesis or hemopoiesis [hemo, (hem"ah-to-poi-e'sis), hemato = blood; poiesis = to make). This process occurs in the red bone marrow, which is composed largely of a soft network of reticular connective tissue bordering on wide blood capillaries called blood sinusoids. Within this network are immature blood cells, macrophages, fat cells, and reticular cells

ferent functions, there are similarities in their

life

(which secrete the fibers). In adults, red marrow is found chiefly in the bones of the axial skeleton and girdles, and in the proximal epiphyses of the humerus and femur. Each type of blood cell is produced in different numbers in response to changing body needs and different regulatory factors. As they mature, they migrate through the thin walls of the sinusoids to enter the bloodstream. On average, the marrow turns out an ounce of new blood containing some 100 billion new cells each and every day.

membrane

Production of Erythrocytes Blood

cell

formation

is

referred to as

d\no3\ouj uiqojBoujau jsd

z

q

jncy

from the same type of stem cell, the pleuripotential hematopoietic stem cell, or hemocytoblast [cyte = cell, blast = bud), which resides in the red bone marrow. However, their maturation pathways differ; and once a cell is committed to a specific blood cell pathway it cannot change. This commitment is signaled by the appearance of histories. All arise

hormones

surface receptors that respond to specific or growth factors, which in turn "push"

the cell toward further specialization. erythropoiesis or production, Erythrocyte (e-rith"ro-poi-e'sis) begins

when

a hemocytoblast

descendant called a myeloid stem cell is transformed into a proerythroblast (Figure 17.5). Proerythroblasts, in turn, give rise to the early (basophilic) erythroblasts that produce huge numbers

During these first two phases, the cells divide many times. Hemoglobin synthesis and iron accumulation occur as the early erythroblast is

of ribosomes.

650

Unit IV

What does

Stem

Maintenance of the Body

the term "committed cell" refer to?

Committed

cell

Developmental pathway

cell

Phase 2 Hemoglobin accumulation

Phase 1 Ribosome synthesis

Hemocytoblast

FIGURE

17.5

Proerythroblast

Early

Late

erythroblast

erythroblast

genesis of red blood cells. Erythropoiesis is a sequence involving proliferation and differentiation of

the bloodstream, and

transformed into a late erythroblast and then a normoblast. The "color" of the cell cytoplasm changes as the blue-staining ribosomes become masked by the pink color of hemoglobin. When a normoblast has accumulated a hemoglobin concentration of about 34%, it ejects most of its organelles. Additionally its nuclear functions end and its nucleus degenerates and is pinched off, causing the cell to collapse inward and assume the biconcave shape.

The

1

the reticulocytes that are released into

result is the reticulocyte. Reticulocytes (essen-

young erythrocytes) are so named because they contain a scant network of clumped ribosomes and rough endoplasmic reticulum. The entire process from hemocytoblast to reticulocyte takes three to five days. The reticulocytes, filled almost to bursting with hemoglobin, enter the bloodstream to begin their task of oxygen transport. Usually they become fully mature erythrocytes within two days of release as their ribosomes are degraded by intracellular enzymes. Reticulocytes account for 1-2% of all erythrocytes in the blood of healthy people. Reticulocyte counts provide a rough index of the rate of RBC formation reticulocyte counts below or above this percentage range indicate abnormal rates of erythrocyte formation. tially

finally

become

j

Ejection of nucleus

Normoblast—

committed red marrow cells through the erythroblast and normoblast stages to

Erythropoiesis:

Phase 3

Reticulocyte

Erythrocyte

erythrocytes. (The myeloid stem

cell,

the

phase intermediate between the hemocytoblast and the proerythroblast, is

not illustrated.)

balance between red blood cell production and destruction. This balance is important because too few erythrocytes leads to tissue hypoxia (oxygen deprivation), whereas too many makes the blood undesirably viscous. To ensure that the number of erythrocytes in blood remains within the homeostatic range, new cells are produced at the incredibly rapid rate of more than 2 million per second in healthy people. This process is controlled hormonally and depends on adequate supplies of iron, amino acids, and certain B vitamins.

still

—

Hormonal Controls

The direct stimulus for provided by erythropoietin (EPO), a glycoprotein hormone. Normally, a small amount of EPO circulates in the blood at all times and sustains red blood cell production at a basal rate (Figure 17.6). Although the -liver produces some, the kidneys play the major role in EPO production. When certain kidney cells become hypoxic (i.e., have inadequate oxygen), they accelerate their release of erythropoietin. The drop in normal blood oxygen levels that triggers EPO formation can result from: erythrocyte formation

1.

Reduced numbers

orrhage or excess

is

of red blood cells

RBC

Regulation and Requirements

2.

for Erythropoiesis

high altitudes or during pneumonia

The number individual

is

of circulating erythrocytes in a given

remarkably constant and

saiAooynaj auj

p

auo }ou

'ai/foojq;/Ga

p

\\ao

poojq

e

a

ue aiucoaq X/uo ueo

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reflects

si

si

uoiiezijepads

\\dO pajj/Luo/oo

y

Reduced

availability of oxygen, as

might occur

Increased tissue demands for oxygen those who engage in aerobic exercise) 3.

due to hem-

destruction at

(common in

Conversely, too many erythrocytes or excessive oxygen in the bloodstream depresses erythropoietin production. The easily missed point to keep in mind is that it is not the number of erythrocytes in blood

Chapter 17

How does blood

doping, practiced by

some

Blood

651

athletes

(see p. 654), affect the negative feedback cycle

outlined here?

Start

Normal blood oxygen

levels

Stimulus: Hypoxia due to decreased RBC count, decreased availability of 0 2

/f

>7b

to blood, or

tissue

increased

demands

for

0„

Increases

02

-

carrying

ability of

blood

Reduces in

02

levels

blood

Kidney (and

Enhanced erythropoiesis

Erythropoietin

increases RBC count

stimulates red

liver to

a smaller

extent) releases erythropoietin

bone marrow

FIGURE 17.6

Erythropoietin mechanism for regulating erythropoiesis. when oxygen levels in the blood become inadequate to support normal cellular activity, whatever the cause. Notice that increased erythropoietin release occurs

that controls the rate of erythropoiesis. Control is based on their ability to transport enough oxygen to

meet

tissue

demands.

Bloodborne erythropoietin stimulates red mar-

row

cells that are

already committed to becoming

erythrocytes, causing

One

to

two days

the blood, a

them

to

mature more

rapidly.

after erythropoietin levels rise in

marked increase

in the rate of reticulo-

hence reticulocyte count) occurs. Notice that hypoxia (oxygen deficit) does not activate the bone marrow directly. Instead it stimulates the kidneys, which in turn provide the hormonal stimulus that activates the bone marrow. cyte release (and

have red blood than half that of healthy individuals. Genetically engineered (recombinant) EPO has helped such patients immeasurably and has also become a particularly in substance of abuse in athletes professional bike racers and marathon runners seeking increased stamina and performance. However, the consequences can be deadly. By injecting EPO, healthy athletes increase their normal RBC volume from 45% to as much as 65%. Then, with the dehydration that occurs in a long race, the blood concentrates even further, becoming a thick, sticky "sludge" that can cause clotting, stroke, and even poiesis. Consequently, they routinely cell

counts

less

—

heart failure.

•

HOMEOSTATIC IMBALANCE sex hormone testosterone also enproduction by the kidneys. Because hances EPO female sex hormones do not have similar stimulatory effects, testosterone may be at least partially responsible for the higher RBC counts and hemoglobin levels seen in males. Also, a wide variety of chemicals released by leukocytes, platelets, and even reticular

The male

Renal dialysis patients whose kidneys have failed produce too little EPO to support normal erythro-

uoi;eujJo/

6uipud Aq asea/aj u/ja/odojuj/Ga

ui

s^gy

sji

jo/ sn/niu/js aqj

p/no/w 'paijodsuejj

pue uoije/nojp p junoiue auj saseajou/ Jdquuinu aq; saseajoui ip/q/w '6uidop poo/g p

Buoq uaBAxo auj

}/q/L/u/

snifi

cells

stimulates bursts of

RBC

production.

652

Maintenance of the Body

Unit IV

How would you change

in

a

expect blood levels of bilirubin to

person that has severe

liver

disease?

Dietary Requirements The raw materials required for erythropoiesis include the usual nutrients and structural materials proteins, lipids, and car-

—

hemoglobin synthesis (Figure 17.7). Iron is available from the diet, and its absorption into the bloodstream is precisely controlled by intestinal cells in response to changing body stores of iron. Approximately 65% of the body's iron supply (about 4000 mg) is in hemoglobin. Most of the remainder is stored in the liver, spleen, and (to a much lesser extent) bone marrow. Because free iron ions

bohydrates. Iron (?)

0 2 levels in blood stimulate kidneys to produce erythropoietin Low

(g) Erythropoietin levels rise in

© raw

blood

and necessary blood promote erythropoiesis in red bone marrow Erythropoietin

materials

in

2+

Fe

is

essential for

3+

are toxic, iron is stored inside cells as protein-iron complexes such as ferritin (fer'i-tin) (Fe

,

)

and hemosiderin (he"mo-sid'er-in). In blood, iron transported loosely (?)

New

erythrocytes

enter bloodstream; function about 1

20 days

in

red

blood cells are engulfed by

and developing erythrocytes take needed to form hemoglobin. Small of iron are lost each day in feces, urine, and as

women

average daily loss of iron

and 0.9

mg in

1.7

is

mg

men. In women, the men-

Two B-complex vitamins

broken down

acid cell

—

vitamin B 12 and folic necessary for normal synthesis.

— are

Thus, even Hemoglobin

DNA

slight deficits jeopardize rapidly dividing

populations, such as developing erythrocytes.

Fate and Destruction of Erythrocytes

Heme

/

Bilirubin

The

strual flow accounts for the additional losses.

macrophages of liver, spleen, and bone marrow; the hemoglobin is

is

to a transport protein

called transferrin,

up iron amounts

perspiration.

(D Aged and damaged

bound

The anucleate condition of erythrocytes carries with it some important limitations. Red blood cells are unable to synthesize new proteins, to grow, or to divide. Erythrocytes become "old" as they lose their

Iron stored

as ferritin, hemosiderin

and become increasingly rigid and fragile, hemoglobin begins to degenerate. Red blood cells have a useful life span of 100 to 1 20 days, after which they become trapped and frag-

flexibility

and Iron is bound and released

from

liver

to transferrin

to blood as needed

ment

in smaller circulatory channels, particularly in those of the spleen. For this reason, the spleen is sometimes called the "red blood cell graveyard." Dying erythrocytes are engulfed and destroyed

for erythropoiesis

picked up from secreted into intestine in bile, metabolized to stercobilin by bacteria and excreted in feces Bilirubin is

blood by

their contained

by macrophages. The heme of their hemoglobin is split off from globin. Its core of iron is salvaged, bound to protein (as ferritin or hemosiderin), and

liver,

stored for reuse.

The balance

degraded to bilirubin

of the

heme group

(bil"i-roo'bin), a

is

yellow pig-

ment that is released to the blood and binds to albumin for transport (Figure 17.7). Bilirubin is picked Circulation

Food

nutrients,

including

amino

acids, Fe,

and

up by liver cells, which in turn secrete it (in bile) into the intestine, where it is metabolized to urobilinogen. Most of this degraded pigment leaves the body in feces, as a brown pigment called stercobilin. The

folic

B 12

,

acid

are absorbed

(D Raw

materials are

made

available

FIGURE

17.7

Life cycle of red

blood

cells.

in

blood for erythrocyte synthesis

from intestine and enter blood

H dje suoiioun} Buissaoojd

s,j3a//

pdjieduji

au) asneoaq aseajou/ p/no/w |

Chapter 17

653

Blood

is metabolized or broken down to amino acids, which are released to the circulation. Disposal of hemoglobin spilled from red blood cells to the blood (as occurs in sickle-cell anemia or hemorrhagic anemia; see below) takes a similar but much more rapid course to avoid toxic

impaired iron absorption. The erythrocytes produced, called microcytes, are small and pale. The

buildup of iron in blood. Released hemoglobin is captured by the plasma protein haptoglobin and the complex is phagocytized by macrophages.

volume expands and can increase by

Erythrocyte Disorders

ever, this iron deficiency illusion, called athlete's

Most erythrocyte

anemia,

protein (globin) part of hemoglobin

disorders can be classified as ane-

mias or polycythemias. The

many

and

varieties

Anemia

(ah-ne'me-ah; "lacking blood")

a condition in which the blood has abnormally low oxygen-carrying capacity. It is a symptom of some disorder rather than a disease in and of itself. Its hallmark is blood oxygen levels that are inadequate to support normal metabolism. Anemic is

individuals are fatigued, often pale, short of breath,

and 1.

chilly.

An

Common causes

insufficient

number

of

anemia

include:

of red blood cells.

Con-

ditions that reduce the red blood cell count include

blood

loss,

marrow

excessive

RBC

destruction, and bone

failure.

Hemorrhagic anemias (hem"o-raj'ik) result from blood loss. In acute hemorrhagic anemia, blood loss is rapid (as might follow a severe stab wound); it is treated by blood replacement. Slight but persistent blood loss (due to hemorrhoids or an undiagnosed bleeding ulcer, for example) causes chronic hemorrhagic anemia. Once the primary problem is resolved, normal erythropoietic mechanisms replace the deficient blood

cells.

In hemolytic anemias (he"mo-lit'ik), erythrocytes

Hemoglobin abnormalmismatched blood, and certain

rupture, or lyse, prematurely. ities,

transfusion of

bacterial

and

parasitic infections are possible causes.

anemia

from destruction or inhibition of the red marrow by certain bacterial toxins, drugs, and ionizing radiation. Because marrow destruction impairs formation of all formed elements, anemia is just one of its signs. Defects in blood clotting and immunity are also present. Blood transfusions provide a stopgap treatment until bone Aplastic

marrow blood,

results

transplants or transfusion of umbilical

which contains stem

cells,

can be done.

result of

anemia

is

generally a secondary

hemorrhagic anemias, but

from inadequate intake

it

also results

of iron-containing foods

and

iron

is is

supplements,

but

if

the cause, blood transfusions

athletes exercise vigorously, their blood as

much

as

blood components, a test for the iron content of the blood at such times would indicate iron-deficiency anemia. How-

15%. Since this in

effect dilutes the

quickly reversed as blood components return to physiological levels within a day or so after is

level of activity.

Pernicious anemia is due to a deficiency of vitamin B 12 Because meats, poultry, and fish pro.

vide ample

amounts

problem except

of the vitamin, diet

for strict vegetarians.

is

A

rarely the

substance

produced by the stomach mucosa, must be present for vitamin B 12 to be absorbed by intestinal cells. In most cases of pernicious anemia, intrinsic factor is deficient. Consequently, the developing erythrocytes grow but do not divide, and large, pale cells called macrocytes result. Because the stomach mucosa atrophies with age, the

called intrinsic factor,

elderly are particularly at risk for this type of anemia.

Treatment involves regular intramuscular injections of vitamin B 12 or application of a B 12 -containing gel (Nascobal) to the nasal lining once a week. 3.

Abnormal hemoglobin. Production

of

abnormal

hemoglobin usually has a genetic basis. Two such examples, thalassemia and sickle-cell anemia, can be serious, incurable, and sometimes fatal diseases. In both diseases the globin part of hemoglobin is abnormal and the erythrocytes produced are fragile and rupture prematurely. Thalassemias (thal"ah-se'me-ahs; "sea blood") are typically seen in people of Mediterranean ancestry, such as Greeks and Italians. One of the globin chains is absent or faulty, and the erythrocytes are thin, delicate,

and

red blood cell count

is

deficient in hemoglobin.

The

generally less than 2 million

most cases the reduced RBC count is not a major problem and no treatment is required. Severe cases require monthly blood cells

per cubic millimeter. In

transfusions.

In sickle-cell anemia, the havoc caused by the abnormal hemoglobin formed, hemoglobin S (HbS),

change in just one of the 287 amino acids in a beta chain of the globin molecule! This alresult

2. Low hemoglobin content. When hemoglobin molecules are normal, but erythrocytes contain fewer than the usual number, a nutritional anemia is always suspected.

Iron-deficiency

When

resuming a normal

causes of these conditions are described next.

Anemias

obvious treatment chronic hemorrhage may also be needed.

from

a

teration causes the beta chains to link together un-

der low- oxygen conditions, forming stiff rods so that hemoglobin S becomes spiky and sharp. This, in turn, causes the red blood cells to

ecules or

when

when

become crescent

they unload oxygen molthe oxygen content of the blood is

shaped (Figure 17.8)

654 FIGURE

Unit IV

17.8

Maintenance of the Body

Comparison of

(a)

a normal erythrocyte to (b) a

sickled erythrocyte (6700X).

(b)

(a)

lower than normal, as during vigorous exercise and other activities that increase metabolic rate. The stiff, deformed erythrocytes rupture easily and tend to dam up in small blood vessels. These events interfere with oxygen delivery, leaving the victims gasping for air and in extreme pain. Bone and chest pain are particularly severe; infection and stroke are common sequels. The standard treatment for an acute sickle-cell crisis is blood transfusion. Sickle-cell anemia occurs chiefly in black people who live in the malaria belt of Africa and among their descendants. It strikes nearly 1 of every 400 black newborns in the United States. Globally, 300-500 million people are infected and more than a million die each year. Apparently, the gene that causes sickling of red blood cells also causes erythrocytes infected by the malaria-causing parasite to stick to capillary walls. Then, during oxygen deficit, these abnormal erythrocytes lose potassium, an essential ingredient for survival of the parasite.

Thus,

Polycythemia vera,

to sludge, or flow sluggishly.

most often a result of bone marrow cancer, is characterized by dizziness and an exceptionally high

RBC

count (8-11 million

The hematocrit may be

cells

per cubic millimeter).

as high as

80% and

blood

volume may double, causing the vascular system to become engorged with blood and severely impairing circulation.

Secondary polycythemias result when less oxygen is available or EPO production increases. The secondary polycythemia that appears in individuals living at high altitudes is a normal physiological response to the reduced atmospheric pressure and lower oxygen content of the air in such areas. RBC counts of 6-8 million per cubic millimeter are common in such people. Severe polycythemia is treated by blood dilution, that is, removing some blood and replacing it with saline. Blood doping, practiced by some athletes competing in aerobic events, is artificially induced poly-

individuals with the sickle-cell gene have a better

cythemia.

Some

chance of surviving in regions where malaria is prevalent. Only those carrying two copies of the defective gene have sickle-cell anemia. Those carrying only one sickling gene have sickle-cell trait; they generally do not display the symptoms, but can transmit the gene to their offspring. Since fetal hemoglobin (HbF) does not "sickle," even in those destined to have sickle-cell anemia, investigators have been looking for ways to switch the fetal hemoglobin gene back on. Hydroxyurea, a drug used to treat chronic leukemia, appears to do just that. This drug dramatically reduces the excruciating pain and overall severity and complications of sickle-cell anemia (by 50%). Additionally, a number

drawn

and then reinjected a few days before the

of the athlete's red blood cells are

event. Because the erythropoietin mechanism is triggered shortly after blood removal, the erythrocytes are quickly replaced.

Then, when the stored blood

is

reinfused, a temporary polycythemia results. Since

red blood cells carry oxygen, the additional infusion

should translate into increased oxygen-carrying capacity due to a higher hematocrit, and hence greater

endurance and speed. Other than problems that might derive from increased blood viscosity, such as temporary high blood pressure or reduced blood delivery to body tissues, blood doping seems to work. However, the practice is considered unethical and has been banned from the Olympic Games.

now

being clinically tested for their effectiveness against this scourge, including several vaccines,- G25, an injectable drug that prevents the parasite's replication; and a small portion of the HIV virus used as a vector to deliver therapeutic A p -globin genes for synthesizing beta chains that resist linking together or polymerization. of products are

off

Polycythemia

Polycythemia (pol"e-si-the'meah "many blood cells") is an abnormal excess of ;

erythrocytes that increases blood viscosity, causing

it

Leukocytes General Structural and Functional Characteristics Leukocytes [leuko = white), or white blood cells (WBCs), are the only formed elements that are complete cells, with nuclei and the usual organelles. Accounting for less than 1% of total blood volume, leukocytes are far less numerous than red blood

Chapter 17

cells.

On

average, there are

cubic millimeter

(mm

3 )

4800-10,800

WBCs

655

Blood

Differential

per

WBC count

of blood.

480010,800/mm 3

(All total

Leukocytes are crucial to our defense against disease. They form a mobile army that helps protect

damage by bacteria, viruses, parasites, toxins, and tumor cells. As such, they have some very special functional characteristics. Red blood the body from

confined to the bloodstream, and they carry out their functions in the blood. But white blood cells are able to slip out of the capillary blood vessels a process called diapedesis (di"ah-pe-de'sis; and the circulatory system is "leaping across") simply their means of transport to areas of the body

)

Formed elements

—

Platelets

Granulocytes Neutrophils (50-70%)

•

cells are

—

-• Eosinophils (2-4%)

— —

—

(mostly loose connective tissues or lymphoid tissues) where they are needed to mount inflammatory or immune responses. As explained in more detail in Chapter 21, the signals that prompt WBCs to leave the bloodstream at specific locations are adhesion molecules (selectins) displayed by endothelial cells forming the capillary walls at sites of inflammation. Once out of the bloodstream, leukocytes move

through the tissue spaces by amoeboid motion (they form flowing cytoplasmic extensions that move them along). By following the chemical trail of molecules released by damaged cells or other leukocytes, a phenomenon called positive chemotaxis, they can pinpoint and gather in large numbers at areas of tissue damage and infection to destroy foreign substances or dead cells. Whenever white blood cells are mobilized for action, the body speeds up their production and twice the normal number may appear in the blood within a few hours. A white blood cell count of over 11,000 cells per cubic millimeter is leukocytosis. This condition is a normal homeostatic response to an infection in the body. Leukocytes are grouped into two major categories on the basis of structural and chemical characteristics: Granulocytes contain obvious membranebound cytoplasmic granules; agranulocytes lack obvious granules. General information about the various leukocytes is provided next. More details appear in Figure 17.9 and Table 17.2.

Students are often asked to

list

the leukocytes in

most abundant to least abundant. The following phrase may help you with this task: Never let monkeys eat bananas (neutrophils, lymphocytes, order from

monocytes, eosinophils, basophils).

Granulocytes Granulocytes

(gran'u-lo-slts),

trophils, basophils,

spherical in shape.

most

which include neu-

and eosinophils, are all roughly are larger and much shorter

They

cases) than erythrocytes. They charachave lobed nuclei (rounded nuclear masses connected by thinner strands of nuclear material), and their membrane-bound cytoplasmic

lived (in

Leukocytes

teristically

Erythrocytes

—

•

Basophils (0.5-1%)

Agranulocytes Lymphocytes (25-45%)

•

•

Monocytes (3-8%)

FIGURE 17.9 Types and relative percentages of leukocytes in normal blood. (The relationship of the formed elements in the left column is not shown to scale because erythrocytes comprise nearly 98% of the formed elements whereas leukocytes and platelets together account for the remaining 2+%.)

granules stain quite specifically with Wright's stain. Functionally, all granulocytes are phagocytes.

Neutrophils

numerous

Neutrophils

(nu'tro-filz),

the

most

of the white blood cells, account for 50 to

WBC

population. Neutrophils are about 70% of the twice as large as erythrocytes. The neutrophil cytoplasm stains pale lilac and contains very fine granules (of two varieties) that are

Table 17.2 and Figure 17.10a). neutrophils (literally, "neutralloving") because their granules take up both basic (blue) and acidic (red) dyes. Together, the two types of granules give the cytoplasm a lilac color. Some of these granules contain hydrolytic enzymes, and are regarded as lysosomes. Others, especially the smaller granules, contain a potent "brew" of antibiotic-like proteins, called defensins. Neutrophil nuclei consist of three to six lobes. Because of this nuclear variability, they are often called polymorphonuclear leukocytes (PMNs) or simply polys (polymorphonuclear = many shapes of the nucleus). (However, some authorities use this term to refer to all granulocytes.) Neutrophils are chemically attracted to sites of inflammation and are active phagocytes. They are difficult to see (see

They

are

called

and some fungi, and bacterial lolling is promoted by a process called a respiratory burst. In the respiratory burst, oxygen is especially partial to bacteria

actively metabolized to produce potent germ-killer

oxidizing substances such as bleach and hydrogen

656

Maintenance of the Body

Unit IV

TABLE

17. 2

^

Summary

of

Formed Elements

of the Blood Duration of

Cells/mm Cell

Type

Erythrocytes blood cells, RBCs)

and D:

million

disc;

diameter 7-8

LS:

Life

(D)

Span

(LS)

5-7 days 100-120

Function

Transport oxygen and carbon dioxide

days

\x.m

Leukocytes

Spherical, nucleated

(white blood

cells

cells,

4-6

Biconcave, anucleate salmon-colored;

(red

Development

(fil)

of Blood

Description*

Illustration

3

4800-10,800

WBCs)

Granulocytes

3000-7000

Nucleus multilobed; inconspicuous

Neutrophil

D:

Phagocytize bacteria

6 hours to a few days

cytoplasmic granules; diameter 10-12 \xm

Nucleus bilobed; red cytoplasmic granules; diameter 10-14 (xm

Eosinophil

6-9 days

LS:

100-400

D: LS:

6-9 days 8-12 days

parasitic

Kill

worms;

destroy antigen-

antibody complexes; inactivate

some

inflammatory chemicals of allergy

Basophi

20-50

granules; diameter

3-7 days few hours to a few

8-10 |xm

days)

contain heparin, an anticoagulant

D: days to

Mount immune

Nucleus lobed; large blue-purple cytoplasmic

D:

Release histamine

LS: ? (a

and other mediators of inflammation;

Agranulocytes

«

Lymphocyte

Monocyte

Platelets /£>

*

LS:

" j,

*Appearance when stained with Wright's

100-700

150,000-400,000

4-5 days 5-10 days

deep

Phagocytosis; develop into

macrophages

Seal small tears

in

in

blood vessels; instrumental

purple; diameter

blood

stain.

It

ap-

of the ingested "foe." Neutrophils

and

their

numbers

increase explosively during acute bacterial infections

such as meningitis and appendicitis. account leukocytes and are approximately

Eosinophils

in

clotting

2-4 |xm

are our body's bacteria slayers,

all

D: LS:

merged with a microbe-containing phagosome,

Eosinophils for 2 to 4% of

2-3 days months

tissues

the granules containing defensins

membrane

D: LS:

the defensins form peptide "spears" that pierce holes in the

cell

to years

Discoid cytoplasmic fragments containing

peroxide, and defensin-mediated lysis occurs.

when

response by direct

attack or via antibodies

jjim

granules; stain

•

hours

^

b>

>

are

weeks

Nucleus U or kidney shaped; gray-blue cytoplasm; diameter

14-24

pears that

1500-3000

Nucleus spherical or indented; pale blue cytoplasm; diameter 5-17 |xm

(e"o-sin'o-filz)

the size of neutrophils. Their deep red nucleus usually resembles an old-fashioned telephone receiver; that

is, it

has two lobes connected by a broad band of

nuclear material (see Table 17.2 and Figure 17.10b). Large, coarse granules that stain from brick red to crimson with acid feosin) dyes pack the cytoplasm. These granules are lysosome-like and filled with a unique variety of digestive enzymes. However, unlike typical lysosomes, they lack enzymes that specifically digest bacteria.

Chapter 17

(b)

(a)

FIGURE 17.10

Leukocytes,

Neutrophil, (b) Eosinophil, (d) Small In

657

Blood

(c)

(a)

Basophil,

lymphocyte, (e) Monocyte.

each case the leukocytes are

surrounded by erythrocytes

(All

1600X). (e)

(d)

The most important

role of eosinophils is to lead

worms, such as and roundworms

the counterattack against parasitic

flatworms (tapeworms and flukes)

(pinworms and hookworms) that are too large to be phagocytized. These worms are ingested in food (especially raw fish) or invade the body via the skin and then typically burrow into the intestinal or respiratory mucosae. Eosinophils reside in the loose connective tissues at the same body sites, and when a

worm

"prey" is encountered, they gather around and release the enzymes from their cytoplasmic granules onto the parasite's surface, digesting it

parasitic

away. Eosinophils also lessen the severity of allergies

by phagocytizing

immune

(antigen-antibody)

com-

plexes involved in allergy attacks and inactivating certain

inflammatory chemicals released during

al-

lergic reactions.

bind to a particular antibody (immunoglobulin E) that causes the cells to release histamine. However, they arise from different cell lines.

Agranulocytes

The agranulocytes cytes,

WBCs

include lymphocytes and

mono-

that lack visible cytoplasmic granules.

Although they are similar structurally, they are functionally distinct and unrelated cell types. Their nuclei are typically spherical or

Lymphocytes

kidney shaped.

Lymphocytes, accounting

for

25%

or more of the WBC population, are the second most numerous leukocytes in the blood. When stained, a typical

lymphocyte has a

that occupies

most

dark-purple nucleus volume. The nucleus is

large,

of the cell

may be slightly indented, and it surrounded by a thin rim of pale-blue cytoplasm (see Table 17.2 and Figure 1 7. lOd). Lymphocyte diameter ranges from 5 to 17 ixm, but they are often classified according to size as small (5-8 |xm), medium (10-12 (xm), and large (14- 17|xm). Although large numbers of lymphocytes exist in the body, only a small proportion of them (mostly the small lymphocytes) is found in the bloodstream. In fact, lymphocytes are so called because most are firmly enmeshed in lymphoid tissues (lymph nodes, spleen, etc.), where they play a crucial role in immunity. T lymphocytes (T cells) function in the immune response by acting directly against virususually spherical but is

Basophils

Basophils are the rarest white blood averaging only 0.5 to 1% of the leukocyte population. Basophils are slightly smaller than neutrophils. Their cytoplasm contains large, coarse histamine-containing granules that have an affinity for the basic dyes [basophil = "base loving") and cells,

stain purplish-black. Histamine is an inflammatory chemical that acts as a vasodilator (makes blood vessels dilate) and attracts other white blood cells to the inflamed site; drugs called antihistamines counter this effect. The deep purple nucleus is generally U or S shaped with two or three conspicuous

constrictions.

infected

Granulated cells similar to basophils, called mast cells, are found in connective tissues. Although mast cell nuclei tend to be more oval than lobed, the cells are similar microscopically, and both cell types

(B cells) give rise to plasma

cells

and tumor

B lymphocytes which produce an-

cells. cells,

tibodies (immunoglobulins) that are released to the T lymphocyte functions are described

blood. (B and

in Chapter 21.)

.

658

Maintenance of the Body

Unit IV

Monocytes Monocytes, which account for 3-8% of WBCs, have an average diameter of 18 |xm and are the largest leukocytes.

They have abundant

pale-blue

cytoplasm and a darkly staining purple nucleus, which is distinctively U or kidney shaped (see Table 17.2 and Figure 17.10e).

When circulating monocytes

leave the

bloodstream and enter the tissues, they differentiate into highly mobile macrophages with prodigious appetites.

Macrophages are

actively phagocytic,

and

they are crucial in the body's defense against viruses, and chronic

certain intracellular bacterial parasites,

As explained in Chapmacrophages are also important in activating lymphocytes to mount the immune response. infections such as tuberculosis. ter 21,

Production and

Life

Span of Leukocytes

Like erythropoiesis, leukopoiesis, or the production

hormonally stimulated. These hormones, released mainly by macrophages and T lymphocytes, are glycoproteins that fall into two families of hematopoietic factors, interleukins and colony-stimulating factors, or CSFs. While the of white

blood

interleukins are

CSFs

named

cells,

is

numbered

(e.g.,

IL-3, IL-5),

—

for the leukocyte

tients.

Figure 17.11 shows the pathways of leukocyte

An early branching of the pathway lymphoid stem cells, which produce lymphocytes, from the myeloid stem cells, which give rise to all other formed elements. In each granulocyte line, the committed cells, called myeloblasts (mi'e-lo-blasts"), accumulate lysosomes, becoming differentiation.

divides the

promyelocytes. The distinctive granules of each granulocyte type appear next in the myelocyte stage and then cell division stops. In the subsequent stage, the nuclei become arc-like, producing the band cell stage. Just before granulocytes leave the marrow and enter the circulation, their nuclei constrict, beginning the process of nuclear segmentation. The bone marrow stores mature granulocytes and usually contains 10 to 20 times more granulocytes than are found in the blood. The normal ratio of granulocytes to erythrocytes produced is about 3:1, which reflects the much shorter life span (0.5 to 9.0 days) of the granulocytes, most of which die combating invading

microorganisms

through monoblast and promonocyte stages

(see

Figure 17.11). Lymphocytes derive from the lymcell and progress through the lymphoblast

phoid stem

and prolymphocyte stages. The promonocytes and prolymphocytes leave the bone marrow and travel to the lymphoid tissues, where their further differentiation occurs (as described in Chapter 21). Monocytes may live for several months, whereas the life span of lymphocytes varies from a few days to decades.

Leukocyte Disorders Overproduction of abnormal leukocytes occurs in leukemia and infectious mononucleosis. At the opposite pole, leukopenia (loo"ko-pe'ne-ah) is an abnormally low white blood cell count {penia = poverty), commonly induced by drugs, particularly glucocorticoids and anticancer agents.

most

population they thus granulocyte-CSF (G-CSF) stimustimulate lates production of granulocytes. The hematopoietic factors not only prompt the white blood cell precursors to divide and mature, but also enhance the protective potency of mature leukocytes. Many of the hematopoietic hormones (EPO and several of the CSFs) are used clinically to stimulate the bone marrow of cancer patients who are receiving chemotherapy (which suppresses the marrow) and of those who have received marrow transplants, and to beef up the protective responses of AIDS paare

Despite their similar appearances, the two types of agranulocytes have very different lineages. Like granulocytes, monocytes diverge from common pleuripotent myeloid stem cells. They then progress

Leukemias

The term leukemia,

"white

literally

blood," refers to a group of cancerous conditions in-

volving white blood cells. As a rule, the renegade leukocytes are members of a single clone (descendants of a single cell) that remain unspecialized and proliferate out of control, impairing normal bone

marrow

function.

The leukemias

are

named

accord-

ing to the abnormal cell type primarily involved. For

example, myelocytic leukemia involves myeloblast descendants, whereas lymphocytic leukemia involves the lymphocytes. Leukemia is acute (quickly advancing) if it derives from blast-type cells like lymphoblasts, and chronic (slowly advancing) if it involves proliferation of later cell stages like myelocytes. The more serious acute forms primarily affect children. Chronic leukemia:is seen more often in elderly people. Without therapy, all leukemias are fatal; only the time course differs. In all leukemias, the bone marrow becomes almost totally occupied by cancerous leukocytes and immature WBCs flood into the bloodstream. Because the other blood cell lines are crowded out, severe anemia and bleeding problems also result. Other symptoms include fever, weight loss, and bone pain.

Although tremendous numbers

FIGURE

17.11

of leukocytes

Leukocyte formation. Leukocytes

from ancestral stem

cells called

Granular leukocytes develop

arise

hemocytoblasts. (a— c)

via a

sequence involving

myeloblasts. The developmental pathway

is

common

until

the granules typical of each granulocyte begin to form, (d-e) Monocytes, like granular leukocytes, are progeny of the myeloid stem cell. Only lymphocytes arise via the

lymphoid stem

cell line.

Chapter 17

Stem

Hemocytoblast

cells

Lymphoid stem

Committed

cell

Lymphoblast

cells

Developmental pathway

Prolymphocyte

Eosinophilic

Neutrophilic

Basophilic

myelocyte

myelocyte

myelocyte

Eosinophilic

Neutrophilic

Basophilic

band

band

band

cells

659

Blood

cells

cells

Monocytes

Lymphocytes (e)

Some Agranular leukocytes

Granular leukocytes

|some become Wandering macrophages

(tissues)

become

660

Unit IV

Stem

Maintenance of the Body

Developmental pathway

cell

J*

Hemocytoblast

Promegakaryocyte

Megakaryoblast

0

Megakaryocyte

Platelets

FIGURE 17.12 Genesis of platelets. The hemocytoblast gives rise to cells that undergo several mitotic divisions unaccompanied by cytoplasmic division to produce megakaryocytes. The cytoplasm of the megakaryocyte becomes compartmentalized by membranes, and the plasma membrane then fragments, liberating the platelets. (Intermediate stages between the hemocytoblast and megakaryoblast are not

illustrated.)

are produced, they are nonfunctional

and cannot

de-

variety of enzymes,

ADP, and platelet-derived growth

fend the body in the usual way. The most common causes of death are internal hemorrhage and over-

factor

whelming

that occurs in plasma

infections.

Irradiation

and administration

of antileukemic

drugs to destroy the rapidly dividing cells have successfully induced remissions (symptom-free periods) lasting

from months

to years.

Bone marrow or um-

cord blood transplants are used in selected patients when compatible donors are available.

bilical

Infectious

Mononucleosis

Once

called

the

(PDGF).

Platelets are essential for the clotting process

when

blood vessels are rupBy sticking to the damaged site, platelets form a temporary plug that helps seal the break. (This mechanism is explained shortly.) Because platelets are anucleate, they age quickly and degenerate in about ten days if they are not involved in clotting. In the meantime, they circulate freely, kept mobile but inactive by molecules (nitric oxide, prostaglandin I 2 secreted by endothelial cells lining the blood vessels. Platelet formation is regulated by a hormone called thrombopoietin. Their immediate ancestral cells, the megakaryocytes, are progeny of the hemocytoblast and the myeloid stem cell, but their formatured or their lining

is

injured.

)

kissing disease, infectious mononucleosis

is

a highly

contagious viral disease most often seen in children and young adults. Caused by the Epstein-Barr virus, its

hallmark

many

of

is

which

excessive

numbers

are atypical.

The

of agranulocytes,

affected individual

complains of being tired and achy, and has a chronic sore throat and a low-grade fever. There is no cure, but with rest the condition typically runs its course to recovery in a few weeks.

Platelets Platelets are not cells in the strict sense.

About

1/4

the diameter of a lymphocyte, they are cytoplasmic cells (up to 60 |xm megakaryocytes (meg"ah-kar'eo-sitz). In blood smears, each platelet exhibits a blue- staining outer region and an inner area

fragments of extraordinarily large in diameter) called

containing granules that stain purple. The granules contain an impressive array of chemicals that act in 2+ the clotting process, including serotonin, Ca a ,

tion

is

quite unusual (Figure 17.12). In this line, re-

peated mitoses of the megakaryoblast occur, but cytokinesis does not. The final result is the megakaryocyte (literally "big nucleus cell"), a bizarre cell with a huge, multilobed nucleus and a large cytoplasmic mass. When formed, the megakaryocyte presses up against a sinusoid (the specialized type of capillary in the marrow) and sends cytoplasmic extensions through the sinusoid wall into the bloodstream. These extensions rupture, releasing the platelet fragments like stamps being torn from a sheet of postage stamps and seeding the blood with

The plasma membranes associated with each fragment quickly seal around the cytoplasm to form the grainy, roughly disc- shaped platelets (see Table 17.2), each with a diameter of 2-4 |xm. Each platelets.

1

Chapter 17

TABLE

17.

3y^

661

Blood

Blood Clotting Factors (Procoagulants)

Factor

Number

Factor

Name

Nature/Origin

Plasma protein; synthesized by

Fibrinogen

I

Function or Pathway

Common

liver

fibrin,

1

Plasma protein; synthesized by formation requires vitamin K

Prothrombin

II

1

III

Tissue factor (TF) or tissue

Lipoprotein complex; released from

damaged

Calcium ions (Ca

IV

21

Common

pathway; converted to thrombin, which enzymatically converts fibrinogen to fibrin

liver;

thromboplastin

'

Activates extrinsic pathway

tissues

Needed

Inorganic ion present in plasma; acquired from diet or released from

)

pathway; converted to weblike substance of clot

for essentially

all

stages

of coagulation process

bone V

Proaccelerin, labile factor, or

Plasma protein; synthesized

platelet accelerator

also released by platelets

Both extrinsic and

in liver;

intrinsic

mechanisms

Number no longer used; now believed to be same as factor V

VI

substance

Proconvertin or serum prothrombin conversion accelerator (SPCA)

VII

Will VIII

Plasma protein; synthesized in

IY IA

Plasma thromboplastin

component (PTC)

Stuart factor, Stuart-Prower factor, or

thrombokinase

Hageman

XII

Plasma protein; synthesized in liver; in hemophilia B; synthesis requires vitamin K

Intrinsic

mechanism

Plasma protein; synthesized

Both extrinsic and pathways

in liver;

synthesis requires vitamin K

Plasma thromboplastin antecedent (PTA)

XI

mechanism

A

deficiency results

or

Christmas factor

X

intrinsic

mechanisms

Intrinsic

Globulin synthesized in liver; deficiency causes hemophilia

Anxinemopniiic Tactor ^Anrj

Both extrinsic and

in liver

process that requires vitamin K

intrinsic

Intrinsic

mechanism

Plasma protein; proteolytic enzyme;

Intrinsic

mechanism; activates

synthesized

plasmin; known to be activated by contact with glass and may

Plasma protein; synthesized in liver; in hemophilia C

deficiency results

factor, glass factor

in

the

liver

initiate clotting in vitro

Plasma protein; synthesized and present in platelets

Fibrin stabilizing factor (FSF)

XIII

cubic millimeter of blood contains between 150,000 and 400,000 of the tiny platelets.

Hemostasis Normally, blood flows smoothly past the intact blood vessel lining (endothelium). But if a blood vessel

wall breaks, a whole series of reactions

motion

to

is

set in

accomplish hemostasis (he"mo-sta'sis),

or stoppage of bleeding {stasis

=

Without this plug-the-hole defensive reaction, we would quickly bleed out our entire blood volume from even halting).

the smallest cuts.

The hemostasis ized,

and

response,

which

is fast,

carefully controlled, involves

many

local-

blood coagulation factors (Table 17.3) normally present in plasma as well as some substances that are released

Cross-links fibrin

in liver

and renders

it

insoluble

by platelets and injured tissue cells. During hemostasis, three phases occur in rapid sequence: 1 vascular spasms, (2) platelet plug formation, and (3) coagulation, or blood clotting. Blood loss at the site is permanently prevented when fibrous tissue grows into the clot and seals the hole in the blood vessel. (

)

Vascular Spasms The immediate response constriction of the

to blood vessel injury

damaged blood

is

vessel (vasocon-

vascular spasm include direct injury to vascular smooth muscle, chemicals released by endothelial cells and platelets, striction). Factors that trigger this

and reflexes initiated by local pain receptors. The spasm mechanism becomes more and more efficient as the amount of tissue damage increases, and is

662

Unit IV

most

Maintenance of the Body

effective in the smaller blood vessels.

value of the spasm response

obvious:

is

A

The

strongly

constricted artery can significantly reduce blood loss

20-30 minutes, allowing time

for

for platelet

plug

Prothrombin activator converts a plasma protein called prothrombin into thrombin, an enzyme. 2.

Thrombin

catalyzes the joining of fibrinogen molecules present in plasma to a fibrin mesh, which 3.

formation and blood clotting to occur.

traps blood cells

Platelet Plug Formation

coagulation process is much more complicated, however. Over 30 different substances are involved. Factors that enhance clot formation are called clotting factors or procoagulants. Although vitamin K is not directly involved in coagulation, this fat-soluble vitamin is required for the synthesis of four of the procoagulants made by the liver (see Table 17.3). Factors that inhibit clotting are called anticoagulants. Whether or not blood clots depends on a delicate balance between these two groups of factors. Normally, anticoagulants dominate and clotting is prevented; but when a vessel is ruptured, procoagulant activity in that area increases dramatically and clot formation begins. The procoagulants are numbered I to XIII (Table 17.3) according to the order of their discovery,- hence the numerical order does not reflect the reaction se2+ quence. Tissue factor (III) and Ca (IV) are usually indicated by their names, rather than by numerals. Most of these factors are plasma proteins made by the liver that circulate in an inactive form in blood until mobilized.

and effectively seals the hole until the blood vessel can be permanently repaired.

The complete

key role in hemostasis by forming a plug that temporarily seals the break in the vessel wall. They also help to orchestrate subsequent events that lead to blood clot formation. These Platelets play a

events are

shown

in

simplified

form

in

Figure

17.13a.

As

each other or to the smooth endothelial linings of blood vessels. However, when the endothelium is damaged and underlying collagen fibers are exposed, platelets, with a rule, platelets do not stick to

the help of a large plasma protein called von Willebrand factor (VWF) synthesized by endothelial cells, adhere tenaciously to the collagen fibers and undergo some remarkable changes. They swell, form spiked processes,

and become

sticky.

Once attached, the platelets are activated by the enzyme thrombin and their granules begin to break

down and

release several chemicals.

Some,

like sero-

tonin, enhance the vascular spasm. Others, like adenosine diphosphate (ADP), are potent aggregating agents that attract more platelets to the area and cause them to release their contents. Thromboxane A2 (throm-boks'an), a short-lived prostaglandin derivative that is generated and released, stimulates both events. Thus, a positive feedback cycle that activates

Phase 1: Two Pathways to Prothrombin Activator Clotting may be initiated by either the intrinsic or the extrinsic pathway (Figure 17.13b), and in the

and greater numbers of platelets to the area begins and, within one minute, a platelet plug is built up, which further reduces blood loss. The platelet plug is limited to the immediate area where it is needed by PGI 2 a prostaglandin produced by the endothelial cells. Also called prostacyclin,

body both pathways are usually triggered by the same tissue-damaging events. Clotting of blood outside the body (such as in a test tube) is initiated only by the intrinsic mechanism. Let's examine the "why" of these differences. A pivotal molecule in bofh mechanisms is PF 3 a

PGI 2

phospholipid associated with the external surfaces of aggregated platelets. Apparently, many intermediates of both pathways can be activated only in the presence of PF 3 In the slower intrinsic pathway, all factors needed for clotting are present in (intrinsic to) the blood. By contrast, when blood is exposed to

and

attracts greater

,

is

a strong inhibitor of platelet aggregation.

Platelet plugs are loosely knit, but

when

reinforced

fibrin threads to act as a "molecular glue" for the aggregated platelets, they are quite effective in sealing the small tears in a blood vessel that occur with normal activity. Once the platelet plug is formed, the next stage, coagulation, comes into play.

by

,

.

an additional

factor released

by injured

cells called

thrombomechanism, which

tissue factor (TF), factor HI, or tissue plastin, the "shortcut" extrinsic

Coagulation

bypasses several steps of the intrinsic pathway,

Coagulation or blood clotting (Figure 17.13a), during which blood is transformed from a liquid to a gel, is a multistep process that leads to its critically important last three phases. 1.

A

complex substance

tor

is

formed.

The

final reactions are:

called

prothrombin activa-

is

triggered.

Each pathway requires ionic calcium and

in-

volves the activation of a series of procoagulants, each functioning as an enzyme to activate the next

procoagulant in the sequence. The intermediate steps of each pathway cascade toward a common intermediate, factor

X (Figure

1 7.

13b).

Once

factor

X

Chapter 17

Intrinsic

pathway -ay

Extrinsic

Vessel endothelium ruptures, exposing

663

Blood

pathway

cell trauma causes release of

Tissue

underlying tissues (e.g.,

collagen)

Injury to lining of

Platelet

Fibrin clot

vessel exposes collagen

plug forms

with trapped

Platelets cling

red blood cells

and

fibers; platelets

adhere

their

Tissue factor (TF)

surfaces provide sites for

mobilization of factors

Collagen

Fibrin

Platelets

fibers

Platelets release chemicals that

make nearby

platelets sticky

Ca 2+ Xa

PF 3 from platelets

-

Calcium and other

and

tissue factor

from

PF3 released by aggregated

clotting

damaged

K

factors

tissue cells

in

VIII

C

platelets

blood

TF/Vll a complex

VIIL

plasma IX a /Vlll a

Coagulation

complex

i Formation of prothrombin

©

activator

©

©

Prothrombin

Fibrinogen (soluble)

»

—/

Thrombin

Fibrin

(insoluble)

Thrombin (a)

(ll

/^Ca^ a)

|

XIII

FIGURE 17.13 blood clotting, 1

-3

Events of platelet plug formation and (a) Simplified

schematic of events. Steps

are the major events of coagulation.

The color

of the

arrows indicates their source or destination: red from tissue,

purple from platelets, and yellow to

fibrin, (b)

Detailed

and events involved platelet plug formation and the intrinsic and extrinsic mechanisms of blood clotting (coagulation). (The subscript

flowchart indicating the intermediates

Cross-linked in

fibrin

polymer

(b)

"a" indicates the activated procoagulant.)

has been activated,

it complexes with calcium ions, PF 3 and factor V to form prothrombin activator. This step is usually the slowest step of the blood clotting process, but once prothrombin activator is present, the clot forms in 10 to 15 seconds.

Phase

2:

Common Pathway

to Thrombin

,

Prothrombin activator catalyzes the transformation of the plasma protein prothrombin to the active enzyme thrombin.

664

Unit IV

Maintenance of the Body

the~mass, compacting the clot and drawing the ruptured edges of the blood vessel more closely together.

Even

as clot retraction

is occurring, vessel healing is Platelet-derived growth factor released by platelet degranulation stimu-

taking

place.

(PDGF) smooth muscle and fibroblasts to divide and rebuild the wall. As fibroblasts form a connective tis-

lates

sue patch in the injured area, endothelial cells, stimulated by vascular endothelial growth factor (VEGF), multiply and restore the endothelial lining.

Fibrinolysis

A clot is not a permanent solution to blood vessel inand a process called fibrinolysis removes unneeded clots when healing has occurred. Because small clots are formed continually in vessels throughout the body, this cleanup detail is crucial. Without fibrinolysis, blood vessels would gradually jury,

become completely

The

critical

enzyme

blocked.

natural "clot buster"

FIGURE 17.14 Scanning electron micrograph of erythrocytes trapped in a fibrin mesh. (3000x)

3:

Common Pathway

Thrombin

catalyzes the polymerization of fibrino-

gen (another plasma protein made by the

liver).

As

the fibrinogen molecules are aligned into long, hairlike,

insoluble fibrin strands, they glue the platelets

together and

make

a

web

that forms the structural

plasma beformed elements that try to

basis of the clot. In the presence of fibrin,

comes

gel-like

and

traps

pass through it (Figure 17.14). In the presence of calcium ions, thrombin also activates factor XIII (fibrin stabilizing factor), a cross-linking

enzyme

that binds the fibrin strands

and strengthens and stabilizes the clot. Clot formation is normally complete within 3 to 6 minutes after blood vessel damage. Because the extrinsic pathway involves fewer steps it is tightly together

more

rapid than the intrinsic pathway; in cases of se-

vere tissue trauma within 15 seconds.

it

can promote

it.

The presence

of a clot in

and around the blood vessel causes the endothelial plasminogen activator (TPA). Activated factor XII and thrombin released during clotting also serve as plasminogen activators. As a result, most plasmin activity is confined to the clot, and any plasmin that strays into the plasma is quickly destroyed by circulating enzymes. Fibrinolysis begins within two days and continues slowly over cells to secrete tissue

Mesh

to the Fibrin

a fibrin-

called plasmin,

propriate signals reach

Phase

is

which is produced when the blood protein plasminogen is activated. Large amounts of plasminogen are incorporated into a forming clot, where it remains inactive until apdigesting

clot

formation

several days until the clot

is

finally dissolved.

Factors Limiting Clot Growth or Formation Factors Limiting Normal Clot Growth

Once

the clotting cascade has begun,

it continues Normally, until a clot is formed. two homeostatic mechanisms prevent clots from becoming unneces-

sarily large: (2)

(

1

)

swift

removal of clotting

factors,

and

inhibition of activated clotting factors. For clot-

ting to occur in the first place, the concentration of

must reach certain critical Clot formation in rapidly moving blood is

activated procoagulants levels.

Clot Retraction and Repair Within 30 to 60 minutes, the clot is stabilized further by a platelet-induced process called clot retraction. Platelets contain contractile proteins (actin

and myosin), and they contract in much the same as muscle cells. As the platelets contract,

manner

they pull on the surrounding fibrin strands, squeezing serum (plasma minus the clotting proteins) from

usually curbed because the activated clotting factors are diluted and washed away. For the same reasons, is hindered when it normally blood. contacts flowing Other mechanisms block the final step in which fibrinogen is polymerized into fibrin by restricting thrombin to the clot or by inactivating it if it escapes into the general circulation. As a clot forms, almost

further growth of a forming clot

Chapter 17

thrombin produced is bound onto the fibrin threads. This is an important safeguard because thrombin also exerts positive feedback effects on the all

of the

coagulation process prior to the common pathway. Not only does it speed up the production of prothrombin activator by acting indirectly through factor V, but it also accelerates the earliest steps of the

pathway by activating platelets. Thus, fibrin effectively acts as an anticoagulant to prevent enlargement of the clot and prevents thrombin from acting elsewhere. Thrombin not bound to fibrin is quickly inactivated by antithrombin III, a protein present in plasma. Antithrombin III and protein C, intrinsic

another protein produced in the activity of other intrinsic

liver,

also inhibit the

pathway procoagulants.

Heparin, the natural anticoagulant contained in basophil and mast cell granules and also produced by endothelial cells, is ordinarily secreted in small

amounts

inhibits thrombin by antithrombin III. Like enhancing most other clotting inhibitors, heparin also inhibits the intrinsic pathway.

into the plasma.

It

the activity of

endothelium is smooth and intact, platelets are prevented from clinging and piling up. Also, antithrombic substances heparin and PGI 2 secreted by the endothelial cells normally prevent platelet adhesion. Additionally, it has been found that vitamin E quinone, a molecule formed in the body when vitamin E reacts with oxygen, is a potent as the

—

—

anticoagulant.

Disorders of Hemostasis Blood clotting is one of nature's most elegant creations, but it sometimes goes awry. The two major disorders of hemostasis are at opposite poles. Thromboembolytic disorders result from conditions that cause undesirable clot formation. Bleeding disorders arise from abnormalities that prevent normal clot formation.

Thromboembolytic Conditions Despite the body's many safeguards,

becomes an embolus (plural, emboli). An embolus ("wedge") is usually no problem until it encounters a blood vessel too narrow for it to pass through; then it becomes an embolism, obstructing the vessel. For example, emboli that become trapped in the lungs (pulmonary embolisms) dangerously impair the ability of the body to obtain oxygen. A cerebral embolism may cause a stroke. Drugs that dissolve blood clots (such as TPA) and innovative medical techniques for removing clots are described in A Closer Look in Chapter 19. Conditions that roughen the vessel endothelium, such as arteriosclerosis, severe burns, or inflammation, cause thromboembolytic disease by allowing platelets to gain a foothold. Slowly flowing blood or blood stasis is another risk factor, particularly in bedridden patients and those taking a long flight in economy-class seats. In this case, clotting factors are not washed away as usual and

accumulate so that

clot

formation finally becomes

possible.

A number

of drugs,

most importantly

aspirin,

heparin, and dicumarol, are used clinically to prevent undesirable clotting in patients at risk for heart

Factors Preventing Undesirable Clotting

As long

665

Blood

attack or stroke. Aspirin is an antiprostaglandin drug that inhibits thromboxane A 2 formation (hence, it blocks platelet aggregation and platelet plug formation). Clinical studies of men taking lowdose aspirin (one aspirin every two days) over several years demonstrated a 50% reduction in (anticipated) incidence of heart attack. Heparin (see above) is also prescribed as an anticoagulant drug, as is warfarin, an ingredient in rat poison. Administered in injectable form, heparin is the anticoagulant most used clinically (i.e., for preoperative and postoperative cardiac patients and for those receiving blood transfusions). Taken orally, warfarin (Coumadin) is a mainstay in the treatment of those prone to atrial fibrillation, a condition in which blood pools in the heart, to reduce the risk of stroke. It works via a different mechanism than heparin; it interferes with the action of vitamin K in the production of some procoagulants (see Impaired Liver Function below).

undesirable in-

travascular clotting, called "hemostasis in the wrong place" by some, sometimes occurs. clot that devel-

A

ops and persists in an unbroken blood vessel is called a thrombus. If the thrombus is large enough, it may block circulation to the cells beyond the occlusion and lead to death of those tissues. For example, if the blockage occurs in the coronary circulation of the heart (coronary thrombosis), the consequences may be death of heart muscle and a fatal heart attack. If the thrombus breaks away from the vessel wall and floats freely in the bloodstream, it

HOMEOSTATIC IMBALANCE Disseminated Intravascular Coagulation Disseminated intravascular coagulation (DIC) is a situation in which widespread clotting occurs in intact blood vessels and the residual blood becomes unable to clot. Blockage of blood flow accompanied by severe bleeding follows. DIC is most commonly encountered as a complication of pregnancy or a result of septicemia or incompatible blood transfusions.

•

666

Unit IV

Maintenance of the Body

LP O Ky?

Concocting Blood:

is

on

that play such

wide

medium

variety of roles

However, substitute liquids are available that can transport oxygen from

body and can

"stretch" a limited blood supply, while

sidestepping transfusion reactions.

for

oxygen.

In

An

body

risk for

ease

that the recipient

is

is

not at

factors.

Four of these oxygen-

transporting products

— PFC-based

compounds, chemically globin,

artificial

Hemopure

altered

red blood

Hemoglobin

— are described

artificial

is

cookware. Developed

monoxide poisonand sickle-cell anemia, its use was clouded by research indicating that Fluosol depressed the immune system. Currently under development is Oxyfluor, a new generation of PFC-based compounds designed to resolve the problems of Fluosol. It has a long shelf life (two years if refrigerated) and delivers up to four times as much oxygen as

product was States

in

first

1982.

recipients

tested

Many

in

promising for therapy of

ing,

briefly.

perfluoro-

used

initially

heart attack, carbon

in

Japan, the

in

they are exhaled as vapor by the

though

carbons (PFCs), compounds similar to Teflon, the nonstick coating

until

and

of Fluosol, a milky

blood substitute,

PFCs are cleared from the circulaand stored in the spleen and liver

lungs 4 to 12 hours after injection. Al-

PFC-Based Compounds The main ingredient

tion

hemo-

cells,

the United

the earlier versions did. However,

of the early

were people who needed

In

their search for substitutes to

oxygen

is

Anything that interferes with the clotting mechanism can result in abnormal bleeding. The most

common

causes are platelet deficiency (thrombocytopenia) and deficits of some procoagulants, which can result from impaired liver function or certain genetic conditions.

A

condition in which the

platelets

is

deficient,

throm-

bocytopenia fthrom"bo-si"to-pe'ne-ah) causes spontaneous bleeding from small blood vessels all over the body. Even normal movement leads to widespread hemorrhage, evidenced by many small purplish blotches, called petechiae (pe-te'ke-e), skin.

Thrombocytopenia can

arise

on the

from any condi-

tion that suppresses or destroys the bone marrow,

such as bone marrow malignancy, exposure to ionizing radiation, or certain drugs. A platelet count of under 50,000 platelets per cubic millimeter of blood

delivery, scientists

boost have found

several ways to alter the chemistry of

hemoglobin:

(1)

create a chemical

bridge between two of chains (cross-link

it,

as

its

in

four peptide

HemAssist);

(2)

hemoglobin molecules together (polymerize hemoglobin, as with several

PolyHeme); or

(3)

attach polyethylene

hemoglobin to stabilize it (as with PHP). The altered hemoglobin gives up more oxygen to the tissues than normal hemoglobin, even at low temperatures (10°C). Since body temglycol (PEG) to

is routinely lowered in patients undergoing heart surgery, using the modified hemoglobin during such procedures might boost oxygen delivery to

perature

the patient's tissues. is

An

additional plus

that the cross-linked form of

globin does not fragment (as natural

in-

creasing the oxygen-carrying capacity of

Bleeding Disorders

Thrombocytopenia number of circulating

causes tissue damage.

Chemically Altered

rate.

transmission of bloodborne dis-

it

sufficient

link

stitutes

tissues,

tients

glide through the capillaries at a faster

important benefit of these blood sub-

blood can have diminishing returns because, when oxygen accumulates in

order to "load"

amounts of oxygen into it, pamust breathe pure oxygen by mask or must be in a hyperbaric (highpressure) chamber. The developers claim that oxygen transported by Fluosol is used more easily by the body tissues because the slippery particles are much smaller than erythrocytes and

no single artificial substitute yet engineered can fulfill all those functions.

the lungs through the

religious grounds.

Fluosol serves as a dissolving

—from fighting infection to transporting oxygen —that

a

Blood Substitutes

surgery but refused blood transfusions

term "blood substitute" The somewhat misleading. Blood has

many components

Artificial

in

hemo-

the blood

hemoglobin does), so the RBC plasma membrane

necessity for a

"container"

is

eliminated.

usually diagnostic for this condition.

Whole blood

transfusions provide temporary relief from bleeding.

Impaired Liver Function

When

the liver

is

un-

usual supply of procoagulants, abnormal, and often severe, bleeding occurs. The causes can range from an easily resolved vitamin K deficiency (common in newborns and after taking systemic antibiotics) to nearly total impairment of liver function (as in hepatitis or cirrhosis). Vitamin K is required by the liver cells for production of the clotting factors, and because vitamin K is produced by bacteria that reside in the intestines, dietary deficiencies are rarely a problem. However, vitamin K deficiency can occur if fat absorption is impaired, because vitamin K is a fat-soluble vitamin that is absorbed into the blood along with fats. In liver disease, the nonfunctional liver cells fail to produce not only the procoagulants but also bile, which is required for fat and vitamin K absorption. able to synthesize

its

Chapter 17

Although there are

still

no plasma membranes to deal

test results are promising,

important problems to be

lem. However, this bovine-based sub-

some

bacte-

stitute

cling to the modified

oxygen delivery more

must address the danger of

transmission of "mad-cow" disease

hemoglobin, and there is some evidence that the free hemoglobin provokes generalized constriction of blood vessels, making ria

and perhaps other not yet

Although the

difficult.

Neohemocytes

FDA

San Francisco have created artificial RBCs, which they call neohemocytes, by packaging natural hemoglobin molecules in fat bubbles made from phospholipids and choles-

RBCs with the harmless polymer PEG to make all blood compatible with all

human neohemodestroyed and cleared more

about one-twelfth the

size of

patients. Researchers are also pro-

bloodstream than are

RBCs, they have a shelf

life

of six

months (versus about 35 days for whole blood). This would make neohemocyte infusion a viable choice for trauma patients in immediate need of blood, but clinical trials on humans are still

in

the distant future.

similar signs

Hemopure Hemopure,

a natural

but

nonhuman

blood substitute recently approved by the FDA, contains purified and polymerized hemoglobin extracted from cattle blood. Because there are

The term hemophilia

Hemophilias

eral different hereditary

for anything but exper-

they had developed a process to coat

erythrocytes. Although the

real

for

imental use in humans. This may change. Early in 1997, researchers at Albany Medical Center reported that

resulting "red cells" are

rapidly from the

blood

including those described above, has

been approved

California at

cytes are

has encouraged

artificial

over 20 years, no marketable product,

Researchers at the University of

The

identified

diseases.

the development of

terol.

with,

cross reactions should not be a prob-

solved. For example, potent poisons

(endotoxins) produced by

667

Blood

ceeding down another path to solve this age-old problem and in 2001 it was documented that stem cells had been converted to RBCs. However, blood still remains a priceless commodity, and its beautiful complexity has yet to be replaced by modern medical technology.

refers to sev-

or injections of the appropriate purified clotting fac-

bleeding disorders that have

These therapies provide relief for several days but are expensive and inconvenient. Because hemophiliacs are absolutely dependent on blood transfusions or factor injections, many have become infected by the hepatitis virus and, since the early 1980s, by HIV a blood-transmitted virus that depresses the immune system and causes AIDS. (See Chapter 21.) This infection problem has been resolved because of new testing methods for HIV and

and symptoms. Hemophilia A, or classifrom a deficiency of factor

cal hemophilia, results

VIII (antihemophilic factor).

It

accounts for

83%

of

Hemophilia B results from a deficiency of factor IX. Both types are sex-linked conditions occurring primarily in males. Hemophilia C, a less severe form of hemophilia seen in both sexes, is due to a lack of fac-

cases.

tor XI. The relative mildness of this form, as compared to the A and B forms, reflects the fact that the procoagulant (factor IX) that factor XI activates may

by factor VII (see Figure 17.13b). hemophilia begin early in life; even minor tissue trauma causes prolonged bleeding into tissues that can be life threatening. Commonly, the

tor.

availability of genetically engineered factor VIII.

also be activated

Symptoms

person's

of

joints

become

seriously

disabled

and

painful because of repeated bleeding into the joint cavities after exercise or trauma. Hemophilias are

managed

clinically

by transfusions of fresh plasma

Transfusion and Blood

Replacement The human

cardiovascular system is designed to minimize the effects of blood loss by 1 reducing the volume of the affected blood vessels, and (2) stepping up the production of red blood cells. However, the (

)

^ 668

Maintenance of the Body

Unit IV

TABLE

17.

4/

ABO

Blood Groups

Frequency (%

U.S. Population)

Blood

Group

White

Asian

Black

RBC

Plasma

Blood

Native

Antigens

Antibodies

That Can Be

American

(Agglutinogens)

(Agglutinins)

Received

None

A, B, AB,

AB

s\/ .'X/paj/pu/

734

Maintenance of the Body

Unit IV

where

who

shed and converted to a biologically active S-nitrosothiol molecule, which causes vasodilation as oxygen is unloaded. Certain other substances released by metabolically active + tissues (such as K H + adenosine, and lactic acid), prostaglandins, and inflammatory chemicals (hista-

throughout the body in people

mine and

pattern of autoregulation. Autoregulation in the brain, heart, and kidneys is extraordinarily efficient. In those organs, adequate perfusion is maintained even when is fluctuating.

tissue capillaries,

,

kinins)

it is

altitude areas,

where the

Blood Flow

in

air

live in high-

contains less oxygen.

Special Areas

,

also

serve

as

autoregulation

stimuli.

Whatever the stimulus, the net bolically controlled autoregulation is

result of

meta-

immediate va-

Each organ has special requirements and functions that are revealed in

its

MAP

sodilation of the arterioles serving the capillary beds of the "needy" tissues,

Skeletal Muscles

crease in blood flow to the area. This

Blood flow in skeletal muscle varies with muscle activity and fiber type. Resting skeletal muscles receive about 1 L of blood per minute, and only about 25% of their capillaries are open. Generally speaking, capillary density and blood flow is greater in red (slow oxidative) fibers than in white (fast glycolytic) fibers. During such periods, myogenic and general neural mechanisms predominate. When muscles become active, blood flow increases (hyperemia) in direct proportion to their greater metabolic activity, a phenomenon called active or exercise hyperemia. The arterioles in skeletal muscle have cholinergic receptors and both alpha and beta (a, p) adrenergic receptors, which bind epinephrine. When epinephrine levels are low, epinephrine mediates vasodilation by binding chiefly to the (3 receptors. Likewise, "occu-

and therefore a temporary inis accompanied by relaxation of the precapillary sphincters, which allows blood to surge through the true capillaries and

become

available to the tissue cells.

Myogenic Controls Inadequate blood perfusion through an organ is quickly followed by a decline in the organ's metabolic rate and, if prolonged, organ death. Likewise, excessively high arterial pressure and tissue perfusion can be dangerous because the combination may rupture the more fragile blood vessels. Such changes in local arteriolar blood pressure and volume are important in autoregulation because they directly stimulate vascular smooth muscle, provoking myogenic responses (myo = muscle; gen = origin). Vascular smooth muscle responds to passive stretch (increased intravascular pressure) with in-

pied" cholinergic receptors are believed to promote vasodilation. Consequently, blood flow

creased tone, which resists the stretch and causes vasoconstriction. Reduced stretch promotes vasodi-

fold or

and increases blood flow into the tissue. Hence, the myogenic mechanism keeps tissue perfusion fairly constant despite most variations in

cles

lation

systemic pressure. Generally, both chemical (metabolic) and physical (myogenic) factors determine the final autoregulatory response of a tissue. For example, reactive hyperemia

more during physical

can increase ten-

activity (see Figure

and virtually all capillaries in the active musopen to accommodate the increased flow. By con-

19.12),

the high levels of epinephrine typical of massive sympathetic nervous system activation (and extremely vigorous exercise involving large numbers of skeletal muscles) cause intense vasoconstriction mediated by the alpha -adrenergic receptors. This protectrast,

tive

response, believed to

(hi"per-e'me-ah) refers to the dramatically increased

chemoreflexes

blood flow into a tissue that occurs after the blood supply to the area has been temporarily blocked. It results both from the myogenic response and from an accumulation of metabolic wastes in the area during occlusion.

low some for

i>e

initiated

when muscle oxygen

critical level,

by muscle

delivery falls be-

ensures that muscle demands

blood do not exceed cardiac pumping ability and

that vital organs continue to receive an adequate

blood supply. Without question, strenuous exercise is one of the most demanding conditions the cardiovascular system faces.

Long-Term Autoregulation the nutrient requirements of a tissue are greater than the short-term autoregulatory mechanism can easily supply, a long-term autoregulation mechaIf

nism may evolve over a period

months to more. The number of

of weeks or

enrich the local blood flow still blood vessels in the region increases, and existing vessels enlarge. This phenomenon, called angiogenesis, is particularly common in the heart when a coronary vessel is partially occluded. It occurs

Muscular autoregulation occurs almost entirely in response to the decreased oxygen concentrations that result from the "rewed-up" metabolism of working muscles. However, systemic adjustments mediated by the vasomotor center must also occur to ensure that blood delivery to the muscles is both faster and more abundant. Strong vasoconstriction of the vessels of blood reservoirs such as those of the digestive viscera and skin diverts blood away from these regions temporarily, ensuring that

more blood

Chapter 19

reaches the muscles. Ultimately, the major factor determining how long muscles can continue to contract vigorously is the ability of the cardiovascular

system to deliver adequate oxygen and nutrients.

The Cardiovascular System: Blood Vessels

735

Below the skin surface are extensive venous plexuses, in which the blood flow velocity can change from 50 ml/min to as much as 2500 ml/min, depending on body temperature. This capability reneural adjustments of blood flow through arterioles and through unique coiled arteriovenous

flects

The Brain Blood flow to the brain averages 750 ml/min and is maintained at a relatively constant level. The necessity for constant cerebral blood flow becomes crystal clear when one takes into account that neurons are totally intolerant of ischemia. Although the brain is the most metabolically active organ in the body, it is the least able to store essential nutrients. Cerebral blood flow is regulated by one of the body's most precise autoregulatory systems and is tailored to local neuronal need. Thus, when you make a fist with your right hand, the neurons in the left cerebral motor cortex controlling that movement receive a more abundant blood supply than the adjoining neurons. Brain tissue is exceptionally sensitive to declining pH, and increased blood carbon dioxide levels (resulting in acidic conditions in brain tissue) cause marked vasodilation. Oxygen deficit is a much less potent stimulus for autoregulation. However, very high carbon dioxide levabolish autoregulatory

els

mechanisms and

severely

depress brain activity.

Besides metabolic controls, the brain also has a

myogenic mechanism that protects it from possibly damaging changes in blood pressure. When MAP declines, cerebral vessels dilate to ensure adequate

brain perfusion.

When MAP

rises, cerebral vessels

constrict, protecting the small,

more

fragile vessels

pathway from rupture due to excesUnder certain circumstances, such as

farther along the sive pressure.

brain ischemia caused by rising intracranial pressure (as

with a brain tumor), the brain

cardiovascular centers) regulates

when

the brain

the medullary

own

its

blood flow

systemic blood pressure. Howsystemic pressure changes are extreme,

by triggering a ever,

(via

becomes vulnerable.

Fainting, or syncope

(sin'cuh-pe; "cutting short"), occurs

when

MAP falls

mm Hg. Cerebral edema the usual result of pressures over 160 mm Hg, which dramatically is

increase brain capillary permeability.

The Skin Blood flow through the skin the

cells,

(2)

higher CNS centers. The arterioles, in addition, are responsive to local and metabolic autoregulatory stimuli.

When

the skin surface

is

exposed to heat, or

body temperature rises for other reasons (such as vigorous exercise), the hypothalamic "thermostat" signals for reduced vasomotor stimulation of the skin vessels. As a result, warm blood flushes into the capillary beds and heat radiates from the skin surface. Vasodilation of the arterioles is enhanced even more when we sweat, because an enzyme in perspiration acts on a protein present in tissue fluid to produce bradykinin, which stimulates the vessel's endothelial cells to release the potent vasodilator NO. When the ambient temperature is cold and body temperature drops, superficial skin vessels are strongly constricted. Hence, blood almost entirely bypasses the capillaries associated with the arteriovenous anastomoses, diverting the warm blood to the deeper, more vital organs. Paradoxically, the skin may stay quite rosy because some blood gets "trapped" in the superficial capillary loops as the shunts swing into operation; also, the chilled skin cells take

up

less

02

.

rise in

below 60

'

anastomoses. These tiny A-V shunts are located mainly in the fingertips, palms of the hands, toes, soles of the feet, ears, nose, and lips. They are richly supplied with sympathetic nerve endings (a characteristic that sets them apart from the shunts of most other capillary beds), and are controlled by reflexes initiated by temperature receptors or signals from

aids in

(

1

)

supplies nutrients to

body temperature regulation,

The Lungs Blood flow through the pulmonary circuit to and from the lungs is unusual in many ways. The pathway is relatively short, and pulmonary arteries and arterioles are structurally like veins and venules. That is, they have thin walls and large lumens. Because resistance to blood flow is low in the pulmonary arterial system, less pressure is needed to propel blood through those vessels. Consequently, arterial pressure in the

pulmonary

circulation

is

for oxygen; the

second and third require neural intervention. The primary function of the cutaneous circulation is to help maintain body temperature, so we will concentrate on the skin's temperature regu-

much lower than in the systemic circulation (24/8 versus 120/80). Another unusual feature of the pulmonary circulation is that the autoregulatory mechanism is the opposite of what is seen in most tissues: Low pulmonary oxygen levels cause vasoconstriction, and

lation function here.

high levels promote vasodilation. While this

provides a blood reservoir. The first function served by autoregulation in response to the need

and is

(3)

may

— 736

Maintenance of the Body

Unit IV

forces blood through the coronary circulation.

normal circumstances, the myoglobin cells stores sufficient

gen needs during

Under

in cardiac

oxygen to satisfy the cells' oxyHowever, an abnormally

systole.

rapid heartbeat seriously reduces the ability of the

myocardium

to receive

adequate oxygen and nutri-

ents during diastole.

Under

resting conditions, blood flow through the

heart is about 250 ml/min and is probably controlled by a myogenic mechanism. During strenuous exercise, the coronary vessels dilate in response to local accumulation of carbon dioxide (leading to acidosis), and blood flow may increase three to four times (see Figure 19.12). Additionally, any event that decreases the oxygen content of the blood causes release of a

02

supply to the 0 2 demand. Consequently, blood flow remains fairly constant despite wide variations (50 to 140 Hg) in coronary perfusion pressure. This enhanced blood flow during increased heart activity is important because under resting conditions, cardiac cells use as

vasodilator that adjusts the

mm

much

65%

oxygen carried to them in blood. (Most other tissue cells use about 25% of the delivered oxygen.) Thus, increasing the blood flow is the only way to make sufficient additional oxygen available to a more vigorously working heart. as

of the

Blood Flow Through Capillaries and Capillary Dynamics

diffusion

through intercellular

Blood flow through capillary networks is slow and intermittent. This phenomenon, called vasomotion, reflects the on/off opening and closing of precapillary sphincters in response to local autoregulatory

cleft

FIGURE 19.14

Capillary transport mechanisms. The

controls.

four possible pathways or routes of transport across the endothelial cell

is

cell wall

drawn as

seem odd,

if

cut

it is

of a fenestrated capillary. (The endothelial in

cross section.)

perfectly consistent

with the gas ex-

role of this circulation. When the air sacs of the lungs are flooded with oxygen-rich air, the pulmonary capillaries become flushed with blood and

change

ready to receive the oxygen load. If the air sacs are collapsed or blocked with mucus, the oxygen content in those areas is low, and blood largely bypasses those nonfunctional areas.

The Heart Movement of

Exchange of Respiratory Gases and Nutrients Capillary

Oxygen, carbon dioxide, most nutrients, and metabolic wastes pass between the blood and interstitial fluid by diffusion. Recall that in diffusion, movement always occurs along a concentration gradient each substance moving from an area of its higher concentration to an area of its lower concentration. Hence, oxygen and nutrients pass from the blood, where their concentration is fairly high, through the

Carbon dioxide and metabolic wastes leave the cells, where their content is higher, and diffuse into the capillary interstitial fluid to the tissue cells.

blood. In general, small water-soluble solutes, such

blood through the smaller vessels of

the coronary circulation

is

influenced by aortic pres-

sure and by the pumping activity of the ventricles. When the ventricles contract and compress the coro-

nary vessels, blood flow through the myocardium stops. As the heart relaxes, the high aortic pressure

as

amino

acids

intercellular

and sugars, pass through capillary

clefts

(and

fluid-filled

sometimes

through fenestrations), while lipid-soluble molecules, such as respiratory gases, diffuse directly through the lipid bilayer of the endothelial cell plasma membranes (Figure 19.14). Newly forming

Chapter 19

How would tial

fluid flows

change

if

the

OP

of the

The Cardiovascular System: Blood Vessels

intersti-

fluid rose dramatically — say because of a severe

bacterial infection

in

the surrounding tissues?

Key

to pressure values:

HP C HP c

at arterial at

end = 35 venous end = 17

mm Hg mm Hg

HP jf

OP c

= 0 mm Hg = 26 mm Hg

OP

FIGURE 19.15

equal to the hydrostatic pressure of the blood (HP C ), which varies along

Fluid flows at The direction of fluid movement depends on the difference between net hydrostatic pressure (HP),

the length of the capillary. Net

(OP c -

OP,f)

is

blood has

much

fact that

content of nondiffusible solutes

capillary.

taken to be zero, net

Because HP

HP (HP C -

lf

HP, f )

is

(net filtration pressure) that

promotes

NFP =

higher

10

mm

Hg. At the venule end of

(proteins) than

the

the bloodstream.

arterial

a

net fluid loss from the capillary:

HP is overpowered by OP (NFP = -8 mm Hg), and fluid returns

the bed,

does interstitial fluid. At end of the capillary bed, net

to

is

some larger molecules, such as small proteins, and pinocytotic vesicles imbibe solute-containing fluid. As mentioned earlier, cap-

caveoli translocate

illaries differ in their

a

mm Hg

HP forcing fluid outward exceeds OP drawing water inward, resulting in a NFP

constant, reflecting the

the capillary, and net colloid osmotic

back into the

1

OP

the force that tends to push fluid out of pressure (OP), the force that draws fluid

= |f

capillaries.

"leakiness," or permeability.

Liver capillaries, for instance, have large fenestra-

allow even proteins to pass freely, whereas brain capillaries are impermeable to most tions

737

that

substances.

two dynamic and opposing forces

— hydrostatic and

colloid osmotic pressures (Figure 19.15).

Hydrostatic Pressures

Hydrostatic pressure

the force exerted by a fluid pressing against a wall. In capillaries, hydrostatic pressure is the same as is

—

the pressure exerted by blood on the capillary walls. Capillary hydrostatic pressure (HP C tends to force fluids through the capillary walls. Because blood pressure drops as blood flows along the length of a capillary bed, HP C is Hg) than higher at the arterial end of the bed (35 Hg). at the venous end 1 7 which forces fluid out In theory, blood pressure is opposed by the interstitial of the capillaries fluid hydrostatic pressure (HP if ) acting outside the

capillary blood pressure

)

Fluid

Movements

All the while nutrient

and gas exchanges are occur-

ring across the capillary walls by diffusion, bulk fluid flows are also going on. Fluid is forced out of the cap-

through the clefts at the arterial end of the bed, but most of it returns to the bloodstream at the venous end. These fluid flows are relatively unimportant to capillary exchange; instead they help determine the relative fluid volumes in the bloodstream and the extracellular space. As described illaries

next, the direction

and amount

of fluid that flows

across the capillary walls reflect the balance

between

mm

(

—

B

p/ny

anss/j

je/j/jsjaju; diji

di\i ui

9Lji ie

—

p jq pajeAa/s

uieujdj p\noN\

uoiiejnojo

mm

dift

paq

atji

Xje///dea at/}

p/aq 'saoeds

p pud

ja;uaaj Ajjjeuipjo p/no/w

snoua/\

}ei/]

p/ny

738

Maintenance of the Body

Unit IV

capillaries

The

static pressure acting

that the

and pushing fluid in. Thus, the net hydroon the capillaries at any point is the difference between HP C and HPjf. However, there

is

usually very

little fluid

in the interstitial space, be-

cause any fluid there is constantly withdrawn by the lymphatic vessels. Although HP,f may vary from slightly negative to slightly positive, traditionally it is assumed to be zero. For simplicity, that is the value we use here. The net effective hydrostatic pressures

and venous ends

bed are essentially equal to HP C (in other words, to blood pressure) at those locations. This information is at the arterial

summarized

of the capillary

in Figure 19.15.

Colloid Osmotic Pressures

Colloid osmotic

pressure, the force opposing hydrostatic pressure,

prevented from moving through the capillary membrane. Such molecules draw water toward themselves; that is, they encourage osmosis whenever the water concentration in their vicinity is lower than it is on the opposite side of the capillary membrane. The abundant plasma proteins in capillary blood (primarily albumin molecules) develop a capillary colloid osmotic pressure (OP c ), also called oncotic pressure, of approximately 26 Hg. Because interstitial fluid contains few proteins, its colloid osmotic pressure (OPjf) is substantially lower from Hg. We use a value of 1 Hg for the 0. 1 to 5 OP in Figure 19.15. Unlike Hp OP does not vary significantly from one end of the capillary bed to the other. Thus, in our example, the net osmotic pressure that pulls fluid back into the capillary blood is Hg = 25 Hg. OP c - OP lf = 26 Hg - 1

mm

mm

—

lt

mm

mm

mm

Hydrostatic-Osmotic Pressure Interactions To determine whether there is a net gain or net loss of fluid from the blood, we have to calculate the net filtration pressure (NFP), which considers all the forces acting at the capillary bed. At any point along net HP is greater than net OP, and fluids will enter the capillary if net OP exceeds net HP. As shown in Figure 19.15, hydrostatic forces dominate at the arterial end (all values are in millimeters of Hg): a capillary, fluids will leave the capillary

NFP - (HP C -

HPif)

-

=

(35

-

0)

=

(35

-

25)

- (OP c -

(26

= 10

-

if

OPif)

1)

(17

-

0)

-

(26

= 17 - 25 = -8

-

1)

mmHg

Circulatory Shock Circulatory shock

any condition in which blood and blood cannot circulate normally. This results in inadequate blood is

vessels are inadequately filled

flow to meet tissue needs. If the condition persists, cells die and organ damage follows.

The most common form

shock is hypovolemic shock (hi"po-vo-le'mik; hypo = low, deficient; volemia = blood volume), which results from large-scale loss of blood, as might follow acute hemorrhage, severe vomiting or diarrhea, or extensive burns.

If

of

blood volume drops rapidly, heart rate

in-

creases in an attempt to correct the problem. Thus, a weak, "thready" pulse is often the first sign of hypovolemic shock. Intense vasoconstriction also occurs, which shifts blood from the various blood reservoirs into the major circulatory channels and enhances venous return. Blood pressure is stable at

but eventually drops if blood loss continues. A sharp drop in blood pressure is a serious, and late, sign of hypovolemic shock. The key to managing

first,

hypovolemic shock

is

to replace fluid

volume

as

quickly as possible.

Although many of the body's responses to hypovolemic shock have yet to be explored, acute bleeding is such a threat to life that it seems important to have a comprehensive flowchart of its recognizable signs and symptoms and an accounting of the body's attempt to restore homeostasis. Figure 19.16 provides such a resource. Study it in part now, and then in more detail later once you have studied the reIn vascular shock, blood

mm Hg (net

excess of HP) is forcing fluid out of the capillary. At the other, venous end, osmotic forces dominate:

NFP =

fluid into the capillary bed. Thus, net fluid flow is our of the circulation at the arterial ends of capillary beds and into the circulation at the venous ends. However, more fluid enters the tissue spaces than is returned to the blood, resulting in a net loss of fluid from the circulation of about 1.5 ml/min. This fluid and any leaked proteins are picked up by the lymphatic vessels and returned to the vascular system, which accounts for the relatively low levels of both fluid and proteins in the interstitial space. Were this not so, this "insignificant" fluid loss would empty your blood vessels of plasma in about 24 hours!

maining body systems.

mm Hg

Thus, in this example, a pressure of 10

NFP

is

created by the presence in a fluid of large nondiffusible molecules, such as plasma proteins, that are

mm

we see here indicates (due to net excess of OP) is driving

negative pressure value

volume

is

normal and

poor circulation as a result of an abnormal expansion of the vascular bed caused by extreme vasodilation. The huge drop in peripheral resistance that follows is revealed by rapidly falling blood pressure. The most common causes of vascular shock are loss of vasomotor tone due to anaphylaxis (anaphylactic shock), a systemic allergic constant, but there

is

Chapter 19

The Cardiovascular System: Blood Vessels

Acute bleeding

(or other

events leading to blood volume loss)

leads to

(T) Inadequate tissue perfusion -» i

0 2 and

nutrients to cells

(2) Cells begin to metabolize anaerobically (without (3)

Water leaves tissue

cells

— moves >

into

02

)

-> lactic acid accumulates

blood -> cells dehydrate

Compensatory mechanisms activated Brain

Chemoreceptors activated (by i in blood pH) major

effect

Baroreceptors

firing

reduced (by 1

in

[

blood volume and blood pressure)

Hypothalamus activated (by i pH and i blood volume) 1

minor^effect

Y

I

respiratory centers

Sympathetic nervous system activated

Cardioacceleratory

Activation of !

and vasomotor centers activated

u

Neurons depressed by I pH

|^Thirs^

Blood pressure maintained*

Restlessness (early sign)

Intense T Heart

T Rate and

vasoconstriction

TJ^HH

depth of

(only heart

and

brain spared)

breathing

Central

Tachycardia, weak, thready pulse

C0 2

blown

blood

pH

!

off;

nervous system depressed

1

rises

Skin

becomes

cold,

clammy, and cyanotic

Coma (late sign)

Adrenal Angiotensin

cortex

produced

in

the blood

i *lf

fluid

volume

continues to decrease, blood pressure ultimately drops. I Blood pressure is a late sign.

Aldosterone released

Kidneys retain salt and water

i Urine output

i Urine output

h

Increased blood volume

FIGURE 19.16 Events and signs of compensated (nonprogressive) hypovolemic shock. (Recognizable clinical signs are shown in red-bordered boxes.)

reaction in which bodywide vasodilation is triggered by the massive release of histamine; failure of autonomic nervous system regulation (also referred to as neurogenic shock); and septicemia (septic shock), a severe systemic bacterial infection (bacterial toxins

Transient vascular shock may occur when you sunbathe for a prolonged time. The heat of the sun on your skin causes cutaneous blood vessels to dilate. Then, if you stand up abruptly blood pools

are notorious vasodilators).

your lower limbs rather than returning promptly to

briefly (because of gravity) in the dilated vessels of

740

Unit IV

Maintenance of the Body |

the heart. Consequently, your blood pressure

The

you

falls.

point is a signal that your brain is not receiving enough oxygen. Cardiogenic shock, or pump failure, occurs when the heart is so inefficient that it cannot sustain dizziness

feel at this

usual cause is myocardial might follow numerous myocardial

adequate circulation.

damage, as

Its

infarcts.

PART 3: CIRCULATORY PATHWAYS: BLOOD VESSELS OF THE BODY When

complex network of the term vascular system is often is

actually a double

pump

that serves two distinct circulations, each with

own

are

named more

vessels.

As

a result,

venous path-

difficult to follow.

4. In most body regions, there is a similar and predictable arterial supply and venous drainage. However, the venous drainage pattern in at least two

important body areas

unique. First, venous blood draining from the brain enters large dural sinuses rather than typical veins. Second, blood draining from the digestive organs enters a special subcirculation, the hepatic portal circulation, and perfuses through the liver before it reenters the general systemic circulation. is

Notice that by convention, oxygen-rich blood is red, while blood that is relatively oxygen-poor is depicted blue, regardless of vessel types. A unique convention used in the schematic flowcharts (pipe diagrams) that accompany each table is that the vessels that would be closer to the viewer are shown in brighter, more intense colors than those deeper or farther from the viewer for example, for veins, the darker blue vessels would be closer to the viewer in

shown

referring to the body's

blood vessels, used. However, the heart

similarly

ways

its

and veins. The pulmonary circulation is the short loop that runs from the heart to the lungs and back to the heart. The systemic circulation routes blood through a long loop to all parts of the body before returning it to the heart. Both circuits are shown schematically in Table 19.3 on p. 744. Except for special vessels and shunts of the fetal circulation (described in Chapter 28), the principal arteries and veins of the systemic circulation are described in Tables 19.4 through 19.13. Although there are many similarities between the systemic arteries and veins, there are also imporset of arteries, capillaries,

—

the body region shown.

Developmental Aspects of the Blood Vessels The

formed by in little masses

endothelial lining of blood vessels

mesodermal

cells,

which

collect

is

by two terminal systemic veins, the superior and inferior venae cavae.

blood islands throughout the microscopic embryo. These then form fragile sprouting extensions that reach toward one another and toward the forming heart to lay down the rudimentary vascular tubes. Meanwhile, adjacent mesenchymal cells, stimulated by platelet-derived growth factor, surround the endothelial tubes, forming the stabilizing muscular and fibrous coats of the vessel walls. It ap-

The

the blood draining

pears that, in arteries at least, the pattern of vessel

from the myocardium of the heart, which is collected by the cardiac veins and reenters the right

branching is orchestrated by vascular endothelial growth factor released by nearby nerves, and forming arteries snuggle closely to those nerves. As noted in Chapter 18, the heart is pumping blood through the rudimentary vascular system by the fourth week of development. In addition to the fetal shunts that bypass the nonfunctional lungs (the foramen ovale and ductus arteriosus), other vascular modifications are found in the fetus. A special vessel, the ductus venosus, largely bypasses the liver. Also important are the

tant differences: 1.

Whereas the heart pumps

single systemic artery

all

of its blood into a

— the aorta — blood returning

to the heart is delivered largely

single exception to this

is

atrium via the coronary sinus.

run deep and are well protected by body tissues along most of their course, but both deep and superficial veins exist. Deep veins parallel the course of the systemic arteries, and with a few 2. All arteries

naming of these veins is identical to companion arteries. Superficial veins

exceptions, the that of their

run

cially

no

beneath the skin and are readily seen, espein the limbs, face, and neck. Because there are

just

names of the superficial do not correspond to the names of any of the

superficial arteries, the

veins

arteries.

Unlike the fairly clear arterial pathways, venous pathways tend to have numerous interconnections, and many veins are represented by not one but two 3.

called

umbilical vein and arteries, large vessels that circulate blood between the fetal circulation and the placenta where gas and nutrient exchanges occur with the mother's blood (see Chapter 28). Once the fetal circulatory pattern is laid down, few vascular changes occur until birth, when the umbilical vessels

and shunts are occluded.

1

Chapter 19

ital

In contrast to congenital heart diseases, congenvascular problems are rare, and blood vessels are

remarkably trouble-free during youth. Vessel formation occurs as needed to support body growth, wound healing, and to rebuild vessels lost each month during a woman's menstrual cycle. As we age, signs of vascular disease begin to appear. In some, the venous valves weaken, and purple, snake-

The Cardiovascular System: Blood Vessels

741

the adult value (120/80). In old age, normal blood pressure averages 1 50/90, which is hypertensive in younger people. After age 40, the incidence of hypertension increases dramatically. Unlike atherosclerosis, which is increasingly important in old age, hypertension claims many youthful victims and is the single most important cause of sudden cardiovascular death in men in their early

veins appear. In others, more insidious signs of inefficient circulation appear: tingling in the fingers and toes and cramping of muscles. Although the degenerative process of athero-

40s and 50s. At least some vascular disease is a product of our modern technological culture. "Blessed" with

consequences are

energy-saving devices, and high-stress jobs, many of us are struck down prematurely. Cardiovascular disease can be prevented somewhat by diet modifications, regular aerobic exercise, and eliminating cigarette smoking. Poor diet, lack of exercise, and smoking are probably more detrimental to your blood vessels than aging itself could ever be!

like varicose

sclerosis begins

in youth,

its

rarely apparent until middle to old age, when it may precipitate a myocardial infarct or stroke. Until pu-

blood vessels of boys and girls look alike, but from puberty to about age 45, women have strikingly less atherosclerosis than men because of berty, the

the protective effects of estrogen, the beneficial effects of which are well documented. By enhancing nitric oxide production, inhibiting endothelin re2+ channels, lease, and blocking voltage-gated Ca estrogen's effect

on blood

vessels

is

to reduce resis-

tance to blood flow. Estrogen also stimulates the produce enzymes that speed up catabolism of LDLs and increase the production of HDLs, thus reducing the risk of atherosclerosis (see A Closer Look). Between the ages of 45 and 65, when estrogen production wanes in women, this "gap" between the sexes closes, and males and females above age 65 are equally at risk for cardiovascular liver to

disease.

Blood pressure changes with age. In a newborn baby, arterial pressure is about 90/55. Blood pressure rises steadily during childhood to finally reach

high-protein, lipid-rich diets, empty-calorie snacks,

*

Now

*

*

we have

described the structure and function of blood vessels, our survey of the cardiovascular system is complete. The pump, the plumbing, and the circulating fluid form a dynamic organ system that ceaselessly services every other organ system of the body, as summarized in Making Connections. However, our study of the socalled circulatory system is still unfinished because we have yet to examine the lymphatic system, which acts with the cardiovascular system to ensure continuous circulation and to provide sites from which lymphocytes can police the body and provide for immunity. These are the topics of that

Chapter 20.

Related Clinical Terms (an'u-rizm aneurysm = a widening) A balloon- • outpocketing of an artery wall that places the artery at risk for rupture; most often reflects gradual weakening of the artery by chronic hypertension or arteriosclerosis. The most common sites of aneurysm formation are the abdominal aorta and arteries feeding the brain and kidneys.

Aneurysm

;

like

(an'je-o-gram"; angio = a vessel; gram = writing) Diagnostic technique involving the infusion of a radiopaque substance into the circulation for X-ray examination of specific blood vessels,- the major technique for diagnosing coronary artery occlusion and risk of a heart attack.

Angiogram

Diuretic {dime = urinate) A chemical that promotes urine formation, thus reducing blood volume; diuretic drugs are frequently prescribed to manage hypertension.

(fle-bi'tis; phleb = vein; ids = inflammation) Inflammation of a vein accompanied by painful throbbing and redness of the skin over the inflamed vessel; most often caused by bacterial infection or local physical trauma.

Phlebitis

Phlebotomy

made

for the

tomy = cut) A venous incision purpose of withdrawing blood or bloodletting.

(fle-bot'o-me;

Sclerotherapy Procedure used for removing varicose or spider veins; tiny needles are used to inject hardening agents into the abnormal vein; the vein scars, closes down, and is

absorbed by the body.

Thrombophlebitis Condition of undesirable intravascular clotting initiated by a roughening of a venous lining; often follows severe episodes of phlebitis. An ever-present danger is that the clot may detach and form an embolus.

742

Unit IV

Maintenance of the Body i

MAKING CONNECTIONS

SYSTEM CONNECTIONS: Homeostatic

Interrelationships

Between

the Cardiovascular System and Other Body Systems

The

ANS

regulates cardiac rate and force; sympa-

blood pressure and blood distribution according to organ need

thetic division maintains

control;

Endocrine System

The cardiovascular system delivers oxygen and nutri ents; carries away wastes; blood serves as a transport vehicle for hormones Various hormones influence blood pressure (epinephrine, ANP, thyroxine, ADH); estrogen maintains vascular health

in

women

Lymphatic System/Immunity

The cardiovascular system

delivers

oxygen and

nutri

immune

cells

ents to lymphatic organs, which house

provides transport

medium

lymphocytes and

for

antibodies; carries away wastes The lymphatic system picks up leaked fluid and plasma proteins and returns them to the cardiovascular system;

its

immune

cells

protect cardiovascular

organs from specific pathogens Respiratory System

The cardiovascular system delivers oxygen and nutrients; carries away wastes The respiratory system carries out gas exchange: loads oxygen and unloads carbon dioxide from the blood; respiratory "pump" aids venous return Digestive System

Integumentary System

The cardiovascular system delivers oxygen and nutrients; carries away wastes The skin vasculature is an important blood reservoir and provides a site for heat loss from the body Skeletal

System

The cardiovascular system delivers oxygen and nutrients; carries away wastes Bones are the sites of hematopoiesis; protect cardiovascular organs by enclosure; and provide a calcium depot

The cardiovascular system delivers oxygen and nutrients; carries away wastes The digestive system provides nutrients to the blood including iron and B vitamins essential for

RBC

(and hemoglobin) formation

Urinary System

The cardiovascular system delivers oxygen and nutrients; carries away wastes; blood pressure maintains kidney function

The urinary system helps regulate blood volume and pressure by altering urine volume and releasing renin

Muscular System

The cardiovascular system delivers oxygen and nutrients; carries away wastes Aerobic exercise enhances cardiovascular efficiency and helps prevent atherosclerosis; the muscle "pump" aids venous return Nervous System

The cardiovascular system delivers oxygen and nutrients; carries away wastes

Reproductive System

The cardiovascular system delivers oxygen and nutrients; carries away wastes Estrogen maintains vascular and osseous health

women

in

THE CARDIOVASCULAR SYSTEM and

CLOSER

CONNECTIONS

The cardiovascular system is the "king of systems." No body system can live without the blood that surges ceaselessly through cardiovascular channels. Likewise,

it

does not influence the cardiovascular system in some way. The respiratory and digestive systems enrich blood with oxygen and nutrients, respectively, and in turn take a share of the various riches the blood has to offer. By returning leaked plasma fluid to the vascular system, the lymphatic system helps to keep those vessels filled with blood so that circulation is possible. However, the is

nearly impossible to find a system that

three cardiovascular system partnerships that we will look at more closely here are those it has with the muscular, nervous, and urinary systems.

Muscular System

about one hand washing the other

Talk

—

that's a pretty

analogy for the interaction between the cardiovascular and muscular systems. Muscles cramp and become nonfunctional when deprived of an adequate supply of

fair

oxygen-rich blood, and their capillary supply expands (or

changes in muscle mass. The arterioles of skeletal muscle even have special beta-adrenergic and ACh receptors so that they can be dilated by neural reflexes when most other body arterioles are responding to vasoconstrictor "orders." When muscles are active and healthy, so too is the cardiovascular system. Without atrophies) along with

exercise, the heart

we

weakens and

loses mass; but

exercise aerobically, the heart increases

strength. Heart rate

and

a lower

size

in

that the heart relaxes

beats hundreds of thousands times less

Aerobic exercise also enhances reduces LDL levels

when

goes down as stroke volume

HR means

— helping

and rises,

more and

a lifetime.

in

HDL blood

levels

and

to clear fatty deposits

from

the vascular walls and deferring atherosclerosis, hypertension,

Interrelationships

with the Muscular, Nervous, and Urinary Systems

and heart disease. Not

a

bad

trade!

Nervous System

The

brain

must have absolutely continuous oxygen and

glucose delivery; thus it should come as no surprise to learn that the brain has the body's most precise autoregulatory circulation mechanism. Acting on acutely sensitive arterioles, this

from most ful,

for

as well.

mechanism protects the brain we can be profoundly thank-

For this

deficits.

when neurons

die,

an important part of us dies

The cardiovascular system

is

just as

dependent

on the nervous system. Although an intrinsic conduction system sets sinus rhythm, it does not even begin to adapt to stimuli that mobilize the cardiovascular system to peak efficiency in maintaining blood pressure during position changes and delivering blood faster during times of stress. This is the job of the autonomic nervous system, which initiates reflexes as necessary to increase or decrease cardiac output and peripheral resistance, and to redirect blood from one organ to others to serve specific needs and protect vital organs. Urinary System Like the lymphatic system, the urinary system (primarily

the kidneys) helps maintain blood volume and circulatory dynamics, but

in

a

much more complicated

The kidneys use blood pressure vascular system) to form the

tubule

cells

(courtesy of the cardio-

filtrate

which the kidney

then process. Essentially

involves reclaiming

needed

way.

nutrients

this

processing

and water while

allowing metabolic waste and excess ions (including H

+ )

body in urine. As a result, blood is continually refreshed and blood composition and volume are carefully regulated. So dedicated are the kidneys to preserving blood volume that urine output stops entirely when blood volume is severely depressed. On the other hand, the kidneys can increase systemic BP by releasing renin when the blood pressure becomes inadequate.

to leave the

CLINICAL

CONNECTIONS Cardiovascular System

middle-aged victim around his thigh when admitted in an unconscious state to Noble Hospital. The emergency technician who brings him in states that his right lower limb was pinned beneath the bus for at least 30 minutes. He is immediately scheduled for surgery. Admission notes include the following:

Case study:

Mr. Hutchinson, another

of the collision

on Route

91, has a tourniquet

fracture of the right tibia;

bone ends

covered with sterile gauze Right leg blanched and cold, no pulse Blood pressure 90/48; pulse 140/min and thready; patient diaphoretic (sweaty)

Relative to

for

tissues 2.

in

the right lower limb?

Will the fracture

be attended

to, or will

homeostatic needs take precedence? Explain your answer choice and predict Mr. Hutchinson's other

his surgical 3.

treatment.

What do you conclude regarding

cardiovascular measurements

Multiple contusions of lower limbs

Compound

what you have learned about tissue oxygen, what is the condition of the requirements 1.

measures do you expect situation before

will

commencing

(pulse

Mr. Hutchinson's

and

BP),

and what

be taken to remedy the with surgery?

(Answers

in

Appendix

F)

744

Maintenance of the Body

Unit IV

TABLE

19.3

/

Pulmonary and Systemic Circulations

Pulmonary Circulation

Pulmonary

The pulmonary

capillaries

R.

of the

artery

circulation (Figure 19.17a) functions

only to bring blood into close contact with the alveoli (air sacs) of the lungs so that gases can be exchanged. It does not directly serve the metabolic needs of body

Pulmonary pulmonary

L.

pulmonary

capillaries

artery

of the

R. lung

L.

lung

tissues.

Oxygen-poor, dark red blood enters the pulmonary it is pumped from the right ventricle into the large pulmonary trunk (Figure 19.17b), which runs diagonally upward for about 8 cm and then divides abruptly to form the right and left pulmonary arteries. In the lungs, the pulmonary arteries subdivide into the lobar arteries (lo'bar) (three in the right lung and two in the left lung), each of which serves one lung lobe. The lobar arteries accompany the main bronchi into the lungs and then branch profusely, forming first arterioles and then the dense networks of pulmonary capillaries that surround and cling to the delicate air sacs. It is here that oxygen moves from the alveolar air to the blood and carbon dioxide moves from the blood to the alveolar air. As gases are exchanged and the oxygen content of the blood rises, the blood becomes bright red. The pulmonary capillary beds drain into venules, which join to form the two pulmonary veins exiting from each lung. The four pulmonary veins complete the circuit by unloading their precious cargo into the left atrium of the heart. Note that any vessel with the term pulmonary or lobar in its name is part of the pulmonary circulation. All others are part of the

circulation as

From systemic circulation

L

pulmonary

veins

(a)

FIGURE 19.17

Pulmonary circulation, (a) Schematic The arterial system is shown in blue

flowchart, (b) Illustration.

to indicate that the blood carried

drainage is

oxygen

is

shown

in

is

oxygen poor; the venous

red to indicate that the blood transported

rich.

systemic circulation.

Left

pulmonary

artery Aortic arch

Pulmonary trunk Right pulmonary artery

Pulmonary Three lobar

capillary

arteries

to right lung

Gas exchange

Pulmonary veins

Two

lobar arteries

to left lung

atrium Left atrium

Chapter 19

TABLE

19.3

2

Pulmonary

(continued)

arteries

carry

oxygen-poor,

carbon

and pulmonary veins carry oxygen-

dioxide-rich blood,

Common

opposite the situation in the systemic circulation, where arteries carry oxygen-rich blood and veins carry carbon dioxide-rich, relatively rich blood.*

745

The Cardiovascular System: Blood Vessels

This

is

carotid arteries to

head and

subclavian

oxygen-poor blood.

arteries to

upper limbs

Systemic Circulation The systemic circulation provides the functional blood supply to all body tissues; that is, it delivers oxygen, nutrients, and other needed substances while carrying

Aortic

arch

away carbon dioxide and other metabolic wastes. Freshly oxygenated blood* returning from the pulmonary circuit is pumped out of the left ventricle into the aorta (Figure 19.18). From the aorta, blood can take various routes, because essentially all systemic arteries branch from this single great vessel. The aorta arches upward from the heart and then curves and runs downward along the body midline to its terminus in the pelvis, where it splits to form the two large arteries serving the lower extremities. The branches of the aorta continue to subdivide to produce the arterioles and, finally, the capillaries that ramify through the organs. Venous blood draining from organs inferior to the diaphragm ultimately enters the inferior vena cava.* Except for some thoracic venous drainage (which enters the azygos system of veins), body regions above the diaphragm are drained by the superior vena cava. The venae cavae empty the carbon dioxide-laden blood into the right atrium of the heart. Two points concerning the two major circulations must be emphasized: (1) Blood passes from systemic veins to systemic arteries only after first moving through the pulmonary circuit (Figure 19.17a), and (2) although the entire cardiac output of the right ven-

passes through the pulmonary circulation, only a small fraction of the output of the left ventricle flows through any single organ (Figure 19.18). The systemic circulation can be viewed as multiple circulatory channels functioning in parallel to distribute blood to all tricle

body organs. As you examine the tables that follow and locate the various systemic arteries and veins in the illustrations, be aware of cues that make your memorization task easier.

In

many

cases, the

name

of a vessel reflects the Inferior

body region traversed (axillary, brachial, femoral, etc.), the organ served (renal, hepatic, gonadal), or the bone

vena cava

followed (vertebral, radial, tibial). Also, notice that arteries and veins tend to run together side by side and, in many places, they also run with nerves. Finally, be alert to the fact that the systemic vessels do not always match on the right and left sides of the body. Thus, while almost all vessels in the head and limbs are bilaterally symmetrical, some of the large, deep vessels of the trunk region are asymmetrical or unpaired.

*By convention, oxygen-rich blood

Venous blood from

is

shown red and oxygen-poor blood

Capillary

beds of

gonads, pelvis, and lower limbs

Schematic flowchart showing an overview of the systemic circulation. The pulmonary circulation is shown in gray for comparison.

FIGURE 19.18

is

shown

blue.

the digestive viscera passes through the hepatic portal circulation

(liver

and associated

veins) before entering the inferior

vena cava.

TABLE

19.4

/

The Aorta and Major Arteries of the Systemic

The

distribution of the aorta and major arteries of the systemic circulation is diagrammed in flowchart form in Figure 19.19a and illustrated in Figure 19.19b. Fine points about the various vessels arising from the aorta are provided in Tables 19.5 through 19.8. The aorta is the largest artery in the body. In adults, the aorta (a-or'tah) is approximately the size of a garden hose where it issues from the left ventricle of the heart. Its internal diameter is 2.5 cm, and its wall is about 2 thick. It decreases in size slightly as it runs to its terminus. The aortic semilunar valve guards the base of the aorta and prevents backflow of blood during diastole. Opposite each semilunar valve cusp is an aortic sinus, which contains baro receptors important in reflex regulation of blood pressure. Different portions of the aorta are named according to shape or location. The first portion, the ascending aorta, runs posteriorly and to the right of the pulmonary trunk. It persists for only about 5 cm before curving to the left as the aortic arch. The only branches

mm

and left coronary which supply the myocardium. The aortic arch, deep to the sternum, begins and ends at the sterof the ascending aorta are the right

arteries,

nal angle (T 4 level). Its three major branches (R to L) are: (1) the brachiocephalic trunk (bra'ke-o-se-fal"ik "armhead"), which passes superiorly under the right clavicle and branches into the right common carotid artery fkah-rot'id) and the right subclavian artery, ;

(2)

the left

subclavian rial supply the thorax runs along

of

,

R. internal

L.

carotid artery

carotid artery

common

carotid artery, and (3) the left These three vessels provide the artethe head, neck, upper limbs, and part of

wall. The thoracic, or descending, aorta the anterior spine from T 5 to T I2 sending off numerous small arteries to the thorax wall and viscera before piercing the diaphragm. As it enters the abdominal cavity, it becomes the abdominal aorta. This portion supplies the abdominal walls and viscera and ends at the L 4 level, where it splits into the right and left common iliac arteries, which supply the pelvis and lower limbs.

R. external

—

common artery.

carotid artery

R.

R. vertebral

Circulation

external

L. internal

carotid artery

carotid

right side of

head and neck

Superior phrenics

— posterior and superior diaphragm

Gonadal

— testes or ovaries

Median sacral

Suprarenal

— adrenal

— sacrum coccyx

glands

and Renal

— kidneys

R.

common

iliac

— pelvis and R. lower limb Arteries of R. lower limb (a)

common

iliac

— Delvis and

L.

lower limb Arteries of

L

lower limb

TABLE

/

19.4

(continued)

FIGURE 19.19 Major arteries of the systemic circulation, (a) Schematic flowchart, (b) Illustration, anterior view.

Internal carotid artery

External carotid artery

Common

carotid arteries

Vertebral artery

Subclavian artery Brachiocephalic trunk Aortic arch Axillary artery

Coronary artery

Ascending aorta Thoracic aorta Brachial artery

Branches

of celiac trunk:

Abdominal aorta

Left gastric artery

Superior mesenteric artery

Splenic artery

Common Gonadal Inferior

Renal artery

artery

mesenteric artery

Common External

artery

iliac

iliac

hepatic artery

artery

Radial artery

Ulnar artery Internal iliac artery

Deep palmar arch Superficial

Digital arteries

Femoral artery

Popliteal artery

Anterior

tibial

Posterior

artery

tibial

Arcuate artery

(b)

artery

palmar arch

748

Maintenance of the Body

Unit IV

TABLE

19.5

2

Arteries of the

Head and Neck

Four paired arteries supply the head and neck. These are the common carotid arteries, plus three branches from each subclavian artery: the vertebral arteries, the thyrocervical trunks, and the costocervical trunks (Figure 19.20b).

Of

these, the

common

carotid arteries

have the broadest distribution (Figure 19.20a).

Each

common

divides

carotid

into

two major

branches (the internal and external carotid arteries). At the division point, each internal carotid artery has a slight dilation, the carotid sinus, that contains baroR.

and

L.

anterior

cerebral arteries

R. middle

cerebral artery

receptors that assist in reflex blood pressure control. The carotid bodies, chemoreceptors involved in the

control of respiratory rate, are located close by. Pressing on the neck in the area of the carotid sinuses can cause

unconsciousness [carot = stupor) because the pressure created mimics high blood pressure, eliciting vasodilation, which interferes with blood delivery to the brain. Description and Distribution carotid arteries. The origins of these two

Common

arteries differ:

The

right

common

carotid artery arises

from the brachiocephalic trunk; the left is the second branch of the aortic arch. The common carotid arteries ascend through the lateral neck, and at the superior border of the larynx (the level of the "Adam's apple"), each divides into its two major branches, the external and internal carotid arteries. The external carotid arteries supply most tissues of the head except for the brain and orbit. As each sends branches to the thyroid gland and larynx (superior thyroid artery), the tongue (lingual artery), the skin and muscles of the anterior artery runs superiorly,

Ophthalmic artery

Superficial

temporal artery

Maxillary artery

Occipital

artery

Facial artery

Lingual artery

Superior thyroid artery

it

and the posterior scalp (occipital Each external carotid artery terminates by splitting into a superficial temporal artery, which supplies the parotid salivary gland and most of the scalp, and a maxillary artery, which supplies the upper and lower jaws and chewing muscles, the teeth, and the nasal cavity. A clinically important branch of the maxillary artery is the middle meningeal artery (not illustrated). It enters the skull through the foramen spinosum and supplies the inner surface of the parietal bone, squamous region of the temporal bone, and the face (facial artery),

artery).

underlying dura mater. The larger internal carotid arteries supply the orbits and more than 80% of the cerebrum. They assume a deep course and enter the skull through the carotid canals of the temporal bones. Once inside the cranium, each artery gives off one main branch, the ophthalmic artery, and then divides into the anterior and middle cerebral arteries.

The ophthalmic

arteries (of-thal'mik)

supply the eyes, orbits, forehead, and nose. Each anterior cerebral artery supplies the medial surface of the frontal

and

parietal lobes of the cerebral

hemisphere

its side and also anastomoses with its partner on the opposite side via a short arterial shunt called the anterior communicating artery (Figure 19.20d). The middle cerebral arteries run in the lateral fissures of their respective cerebral hemispheres and supply the lateral parts of the temporal, parietal, and frontal

on

lobes.

Vertebral arteries. These vessels spring from the subclavian arteries at the root of the neck and ascend through foramina in the transverse processes of the cervical vertebrae to enter the skull through the foramen magnum. En route, they send branches to the vertebrae and cervical spinal cord and to some deep structures of the neck. Within the cranium, the right and left vertebral arteries join to form the basilar artery (bas'i-lar), (a)

Chapter 19

TABLE 19

=2

749

(continued)

which ascends along the anterior aspect

of the brain

stem, giving off branches to the cerebellum, pons, and inner ear (Figure 19.20b and d). At the pons-midbrain border, the basilar artery divides into a pair of posterior cerebral arteries, which supply the occipital lobes and the inferior parts of the temporal lobes. Arterial shunts called posterior communicating arteries connect the posterior cerebral arteries to the middle cerebral arteries anteriorly. The two posterior

and

The Cardiovascular System: Blood Vessels

single anterior

communicating

arteries

complete

the formation of an arterial anastomosis called the This structure encircles the pituitary gland and optic chiasma and unites the brain's anterior and posterior blood supplies. It also equalizes blood pressure in the two brain areas and provides alternate routes for blood to reach the brain tissue if a carotid or vertebral artery becomes occluded. circle of Willis.

Thyrocervical and costocervical trunks. These short from the subclavian artery just lateral to the vertebral arteries on each side (Figures 19.20b and Figure 19.21). The thyrocervical trunk mainly supplies

vessels arise

the thyroid gland, portions of the cervical vertebrae and spinal cord, and some scapular muscles. The costocervical trunk serves deep neck and superior intercostal

muscles.

Ophthalmic artery Superficial

temporal artery Basilar artery

Maxillary artery

(c)

Occipital artery

Facial artery

carotid artery

Lingual artery External carotid artery

Common carotid artery

Thyrocervical trunk

Arteriograph of the

arterial

supply of the

Major arteries serving the brain and circle of Willis. In this inferior view of the brain, the right side of the cerebellum and part of the right temporal lobe have been removed to show the distribution of the middle and brain, (d)

Vertebral artery Internal

FIGURE 19.20 Arteries of the head, neck, and brain, (a) Schematic flowchart. (b) Arteries of the head and neck, right aspect.

Superior thyroid artery

posterior cerebral arteries.

Larynx Thyroid gland (overlying trachea)

Costocervical trunk

Clavicle (cut)

Subclavian artery Axillary

artery

—

Brachiocephalic trunk Internal thoracic

artery

Anterior

(b)

Frontal lobe

—

Circle of Willis •

Optic chiasma

Anterior

communicating artery

Middle

•

cerebral

Anterior

cerebral artery

artery Internal

carotid •

artery

Posterior

communicating

Pituitary

artery

gland •

Temporal

Posterior

cerebral artery

lobe Basilar artery

Pons Occipital

Vertebral artery

lobe

Cerebellum

(c)

(d)

750

Maintenance of the Body

Unit IV

TABLE

19.6

y

Arteries of the

The upper limbs

Upper Limbs and Thorax

are supplied entirely

by

branches of the subclavian arteries. Most visceral organs of the thorax receive their functional blood supply from small branches issuing from the thoracic aorta. Because these vessels are so small and tend to vary in number (except for the bronchial arteries), they are not illustrated in Figures 19.21a and b, but several of them

arteries aris-

ing from the subclavian arteries (Figure 19.21a). After giving off branches to the neck, each subclavian artery courses laterally between the clavicle and first rib to enter the axilla,

where

The thorax wall

name changes

its

to axillary artery.

supplied by an array of vessels that arise either directly from the thoracic aorta or from is

are listed at the

end

of this table.

Description and Distribution R. R. vertebral artery

common

carotid

L.

common

carotid

artery

artery

Thyrocervical

L.

vertebral artery

trunk L.

Arteries of the

Axillary artery.

subclavian

Suprascapular artery

R. subclavian artery

Upper Limb As it runs through the

accompanied by cords

axilla

of the brachial plexus,

each axillary artery gives off branches to the axilla, chest wall, and shoulder girdle. These branches include the thoracoacromial artery (tho"rah-ko-ah-kro'me-al), which supplies the muscle and pectoral region,- the lateral thoracic artery, which serves the lateral chest wall and breast; the subscapular artery to the scapula, dorsal thorax wall, and part of the latissimus dorsi muscle; and the anterior and posterior circumflex humeral arteries, which wrap around the humeral neck and help supply the shoulder joint and the deltoid muscle. As the axillary artery emerges from the axilla, it becomes the brachial artery. deltoid

Axillary artery

Superior thoracic artery

Thoracoacromial Costocervical

artery

trunk Anterior

and posterior circumflex

humeral arteries

Brachial artery

Deep brachial

Posterior

artery

intercostal

Brachial artery. The brachial artery runs down the medial aspect of the humerus and supplies the anterior flexor muscles of the arm. One major branch, the deep brachial artery, serves the posterior triceps brachii muscle. As it nears the elbow, the brachial artery gives off several small branches that contribute to an anastomosis serving the elbow joint and connecting it to the arteries of the forearm. As the brachial artery crosses the anterior midline as-

arteries

pect of the elbow, it provides an easily palpated pulse point (brachial pulse) (see Figure 19.11). Immediately beyond the elbow, the brachial artery splits to form the radial and ulnar arteries, which more or less follow the course of similarly named bones down the length of the anterior forearm.

Radial artery. The radial artery runs from the median line of the cubital fossa to the styloid process of

Radial

the radius. It supplies the lateral muscles of the forearm, the wrist, and the thumb and index finger. At the root of the thumb, the radial artery provides a convenient site for talcing the radial pulse.

artery

Ulnar Deep-

Superficial

palmar

palmar

arch

arch

Metacarpal arteries •Digital

arteries (a)

artery.

The ulnar

artery supplies the medial

aspect of the forearm, fingers 3-5, and the medial aspect of the index finger. Proximally the ulnar artery gives off a short branch, the common interosseous artery (in"ter-os'e-us), which runs between the radius and ulna to serve the deep flexors and extensors of the forearm.

Palmar arches. In the palm, branches of the radial and ulnar arteries anastomose to form the superficial and deep palmar arches. The metacarpal arteries and the

Chapter 19

TABLE

19.6

2

The Cardiovascular System: Blood Vessels

751

(continued)

Common

carotid

arteries

Vertebral artery

Right subclavian

Thyrocervical trunk

artery

Costocervical trunk

Left subclavian

artery

Suprascapular artery Left axillary

Thoracoacromial artery

artery

Axillary artery

trunk

Brachiocephalic

Subscapular artery Posterior circumflex

Posterior

humeral artery

intercostal arteries

Anterior circumflex

Anterior intercostal

humeral artery

artery

Internal thoracic

Brachial artery

artery

Deep

brachial

Lateral thoracic

artery

artery

Descending aorta

Common

interosseous

FIGURE

artery

thorax,

19.21 Arteries of the right upper limb and Schematic flowchart, (b) Illustration.

(a)

Radial artery

Ulnar artery

twiglike branches to the anterior abdominal wall and diaphragm.

•Deep palmar arch Superficial palmar arch Digitals

(b)

Posterior intercostal arteries. The superior two pairs of posterior intercostal arteries are derived from the costocervical trunk. The next nine pairs issue from the thoracic aorta and course around the rib cage to anastomose anteriorly with the anterior intercostal arteries. Inferior to the 12th rib, a pair of subcostal arteries emerges from the thoracic aorta (not illustrated). The posterior intercostal arteries supply the posterior intercostal spaces, deep muscles of the back, vertebrae, and spinal cord. Together, the posterior and anterior intercostal arteries supply the intercostal muscles.

Superior phrenic arteries. One or more paired supephrenic arteries serve the posterior superior aspect

rior

digital arteries that supply the fingers arise

from these

of the

diaphragm

surface.

palmar arches.

Arteries of the Thoracic Viscera

Arteries of the Thorax Wall

Several tiny branches supply the Pericardial arteries. posterior pericardium.

Internal thoracic arteries. The internal thoracic arteries, also called the mammary arteries, arise from the subclavian arteries and supply blood to most of the anterior thorax wall. Each of these arteries descends lateral to the sternum and gives off anterior intercostal arteries, which supply the intercostal spaces anteriorly The internal thoracic artery also sends superficial branches to the skin and mammary glands and terminates in

Bronchial arteries. Two left and one right bronchial arteries supply systemic (oxygen-rich) blood to the lungs, bronchi,

and pleurae.

Esophageal arteries.

Four to

five

esophageal arteries

supply the esophagus.

Mediastinal arteries. ies

Many

small mediastinal arter-

serve the posterior mediastinum.

752

TABLE

Unit IV

19.7

/

Maintenance of the Body

Arteries of the

Abdomen

The

arterial supply to the abdominal organs arises from the abdominal aorta (Figure 19.22a). Under resting conditions, about half of the entire arterial flow is found in these vessels. Except for the celiac trunk, the superior and inferior mesenteric arteries, and the

median

sacral artery, all are paired vessels.

arteries

Gonadal arteries

Inferior

mesenteric artery

Lumbar arteries

Median sacral

artery

Common

arteries

(a)

FIGURE

1

9.22

Arteries of the

abdomen,

(a)

These

arter-

supply the abdominal wall, diaphragm, and visceral organs of the abdominopelvic cavity. The branches are given here in order of their issue. ies

Schematic flowchart.

iliac

Chapter 19

TABLE

/

19.7

Description

and

The Cardiovascular System: Blood Vessels

(continued)

Distribution

phrenic arteries. The inferior phrenics emerge from the aorta at T 12 just inferior to the diaphragm. They serve the inferior diaphragm surface. Celiac trunk. This very large unpaired branch of the abdominal aorta divides almost immediately into three branches: the common hepatic, splenic, and left gastric Inferior

,

The common hepatic artery branches to the stomach, duodenum, and pancreas. Where the gastroduodenal artery branches off, it becomes the hepatic artery proper, which splits into right and left branches that serve the arteries (Figure 19.22b).

(he-pat'ik) gives off

As the splenic artery (splen'ik) passes deep to the stomach, it sends branches to the pancreas and stomach and terminates in branches to the spleen. The left gastric artery [gaster = stomach) supplies part of the stomach and the inferior esophagus. The right and left gastroepiploic arteries (gas"tro-ep"i-plo'ik), branches of the gastroduodenal and splenic arteries, respectively, serve the left (greater) curvature of the stomach. A right gastric artery, which supplies the stomach's right liver.

(lesser)

may arise from the common hepatic from the hepatic artery proper.

curvature,

artery or

Diaphragm

Liver (cut) Inferior

vena cava

Esophagus

Celiac trunk Left gastric artery

Hepatic artery proper

Left gastroepiploic

artery

Common

hepatic artery

Splenic artery Right gastric artery

Gallbladder

Spleen

Gastroduodenal artery

Stomach

Right gastroepiploic

Pancreas

artery

(major portion

Superior mesenteric

Abdominal aorta

artery

(b)

FIGURE its

1

9.22 (continued)

major branches.

lies

posterior to stomach)

Duodenum

Arteries of the

abdomen,

(b)

The

celiac trunk

and

754

TABLE

Unit IV

19.7

Maintenance of the Body

Arteries of the

Abdomen

(continued)

Superior mesenteric artery (mes-en-ter'ik). This large, unpaired artery arises from the abdominal aorta at the Lj level immediately below the celiac trunk (Figure 19.22d). It runs deep to the pancreas and then enters the mesentery, where its numerous anastomosing branches serve virtually all of the small intestine via the intestinal arteries, and most of the large intestine the appendix, cecum, ascending colon (via the ileocolic artery), and part of the transverse colon (via the right and middle colic arteries). Suprarenal arteries (soo"prah-re'nal). The suprarenal arteries flank the origin of the superior mesenteric artery as they emerge from the abdominal aorta (Figure

—

19.22c).

They supply blood

to the adrenal (suprarenal)

glands overlying the kidneys.

Renal arteries. The short but wide renal arteries, right and left, issue from the lateral surfaces of the aorta slightly below the superior mesenteric artery (between Lj and L 2 Each serves the kidney on its side. Gonadal arteries (go-na'dul). The paired gonadal arteries are called the testicular arteries in males and the ).

ovarian arteries in females. The ovarian arteries extend into the pelvis to serve the ovaries and part of the uterine tubes. The much longer testicular arteries

descend through the pelvis and inguinal canal to enter the scrotal sac, where they serve the testes. Inferior mesenteric artery. This final major branch of the abdominal aorta is unpaired and arises from the anterior aortic surface at the L 3 level. It serves the distal part of the large intestine from the midpart of the transverse colon to the midrectum via its left colic, sigmoidal, and superior rectal branches (Figure 19.22d). Looping anastomoses between the superior and inferior mesenteric arteries help ensure that blood will continue to reach the digestive viscera in cases of trauma to one of these abdominal arteries. Lumbar arteries. Four pairs of lumbar arteries arise from the posterolateral surface of the aorta in the lumbar region. These segmental arteries supply the poste-

—

rior

abdominal

Median

—

wall.

The unpaired median sacral from the posterior surface of the abdomiits terminus. This tiny artery supplies the

sacral artery.

artery issues

nal aorta at

sacrum and coccyx.

Common

iliac arteries.

splits into the right

and

At the L 4 left

level,

common

the aorta

iliac arteries,

which supply blood to the lower abdominal organs, and lower limbs (Figure 19.22c).

wall, pelvic

Chapter 19

TABLE

19.7

2

The Cardiovascular System: Blood Vessels

(continued)

Foramen

Diaphragm

-

for inferior

vena cava

Inferior

phrenic

artery

Hiatus (opening) for

esophagus

Suprarenal artery

Celiac trunk

Renal artery Kidney Superior mesenteric artery

Lumbar

arteries

Gonadal

(testicular

or ovarian) artery

Abdominal aorta

Inferior

mesenteric artery

Median sacral

Common

iliac

artery

artery

Ureter (c)

Transverse colon Celiac trunk

Superior mesenteric artery

Middle colic artery Intestinal arteries

Left colic artery

Right colic artery Inferior

mesenteric artery

Ileocolic artery

Aorta

Sigmoidal arteries

Ascending colon

Descending colon Ileum

Superior rectal

Left

common

iliac

artery

artery

Sigmoid colon

Cecum

Rectum

Appendix

(d)

FIGURE 19.22 (continued)

Arteries of the

abdomen,

(c)

Major branches of

the abdominal aorta, (d) Distribution of the superior and inferior mesenteric arteries.

(The transverse colon has been reflected superiorly to provide a better view

of these arteries.)

755

756

Unit IV

TABLE 19

2

At the

Maintenance of the Body

Arteries of the Pelvis and

level of the sacroiliac joints, the

arteries divide into

and external

Lower Limbs

common

iliac

Abdominal

two major branches, the internal

iliac arteries (Figure 19.23a).

The

aorta

internal Superior

blood mainly to the pelvic region. The external iliacs serve the lower limbs; they also send some branches to the abdominal wall. iliacs distribute

Description

and

gluteal

artery Internal iliac

Distribution

artery

Internal iliac arteries. These paired arteries run into the pelvis and distribute blood to the pelvic walls and viscera (bladder, rectum, uterus, and vagina in the female and prostate gland and ductus deferens in the male). Additionally they serve the gluteal muscles via the superior and inferior gluteal arteries, adductor muscles of the medial thigh via the obturator artery, and external genitalia and perineum via the internal pudendal artery (not illustrated).

External iliac arteries. These arteries supply the lower limbs (Figure 19.23b). As they course through the pelvis, they give off branches to the anterior abdominal wall. After passing under the inguinal ligaments to enter the thigh, they become the femoral

Inferior

gluteal

artery Internal

pudendal Medial circumflex

femoral artery

Lateral

circumflex

femoral artery

arteries.

arteries. As each of these arteries passes the anteromedial thigh, it gives off several branches to the thigh muscles. The largest of the deep branches is the deep femoral artery (also more simply called deep artery of the thigh) that is the main supply to the thigh muscles (hamstrings, quadriceps, and adductors). Proximal branches of the deep femoral artery, the lateral and medial circumflex femoral arteries, encircle the neck of the femur. The medial circumflex artery supplies the head and neck of the femur. A long descending branch of the posterior circumflex artery supplies the vastus lateralis muscle. Near the knee the femoral artery passes posteriorly and through a gap in the adductor magnus muscle, the adductor hiatus, to enter the popliteal fossa, where its name

Femoral

down

—

Arterial

anasto-

mosis

Posterior

tibial

artery

changes to popliteal artery. Popliteal artery. This posterior vessel contributes to an arterial anastomosis that supplies the knee region and then splits into the anterior and posterior tibial ar-

Fibular

(peroneal) artery

teries of the leg.

Anterior tibial artery. The anterior tibial artery runs through the anterior compartment of the leg, supplying the extensor muscles along the way. At the ankle, it becomes the dorsalis pedis artery, which supplies the ankle and dorsum of the foot, and gives off a branch, the arcuate artery, which issues the metatarsal arteries to the metatarsus of the foot. The superficial dorsalis pedis ends by penetrating into the sole where it forms the medial part of the plantar arch. The dorsalis pedis artery provides a clinically important pulse point, the pedal If the pedal pulse is easily felt, it that the blood supply to the leg is good.

pulse.

is fairly

Lateral

plantar artery Lateral

plantar

Medial

artery

plantar artery

Arcuate artery

Plantar arch

certain

Posterior tibial artery. This large artery courses through the posteromedial part of the leg and supplies the flexor muscles. Proximally, it gives off a large branch, the fibular (peroneal) artery, which supplies the lateral

Metatarsal

Digital

arteries

arteries

(a)

FIGURE 19.23 limb,

(a)

Arteries of the right pelvis and lower Schematic flowchart.

Chapter 19

TABLE

19.8

2

The Cardiovascular System: Blood Vessels

757

(continued)

fibularis (peroneal)

muscles of the

leg.

At the ankle, the and medial

posterior tibial artery divides into lateral

plantar arteries that serve the plantar surface of the The lateral plantar artery forms the lateral end of the plantar arch. The digital arteries serving the toes arise from the plantar arch formed by the lateral plan-

foot.

Common

iliac

artery

Internal iliac artery

tar artery. Superior gluteal artery External

iliac

Deep femoral

artery

artery

Lateral circumflex femoral artery

Popliteal

artery

Medial circumflex femoral artery Obturator artery

Anterior tibial

Femoral artery

artery

Fibular

Adductor hiatus

Posterior

artery

tibial

artery Popliteal artery

Lateral

plantar artery

Dorsalis pedis artery (from top of foot)

Anterior

tibial

artery

Medial plantar artery

Posterior

tibial

artery (c)

Fibular artery

Dorsalis pedis artery

Arcuate artery Metatarsal arteries

(b)

FIGURE 19.23 (continued)

Arteries of the right pelvis and lower limb. view of the leg and foot.

(b) Illustration, anterior view, (c) Posterior

Plantar arch

.

TABLE

19.9

y

The Venae Cavae and the Major Veins of the Systemic

Circulation

of the right and left brachiocephalic veins and empties into the right atrium (Figure 19.24b). Notice that there are two brachiocephalic veins, but only one brachiocephalic artery (trunk). Each brachiocephalic vein is formed by the joining of the internal jugular and subclavian veins on its side. In most of the flowcharts that follow, only the vessels draining blood from

union

In our survey of the systemic veins, the major tributaries (branches) of the venae cavae are noted first in Figure 19.24, followed by a description in Tables 19.10 through 19.13 of the venous pattern of the various body regions. Because veins run toward the heart, the most distal veins are named first and those closest to the heart last. Because deep veins generally drain the same areas served by their companion arteries, they are not described in detail.

the right side of the body are followed (except for the azygos circulation of the thorax)

The widest blood

Inferior vena cava.

Description and Areas Drained

vessel in the

body, this vein returns blood to the heart from all body regions below the diaphragm. The abdominal aorta lies

Superior vena cava. This great vein receives systemic blood draining from all areas superior to the diaphragm, except the heart wall. It is formed by the

The distal end of the inferior vena formed by the junction of the paired common iliac veins at L 5 From this point, it

directly to its

cava

left.

is

.

Veins of R. upper

R. external

R. vertebral

Intracranial

jugular

-

dural sinuses

-

limb

superficial

head and neck

cervical spinal

cord and vertebrae

I

R. internal

jugular

-

-

dural sinuses of the brain

R. subclavian R. axillary

courses superiorly along the anterior aspect of the spine, receiving venous blood draining from the abdominal walls, gonads, and kidneys. Immediately above the diaphragm, the inferior vena cava ends as it enters the inferior aspect of the right atrium.

R. head, neck,

and upper

Same

as R. brachiocephalic

limb

R. brachiocephalic

-

R. side of

L.

head and

R.

-

upper limb

brachiocephalic L.

side of head and

L

upper limb

Azygos system - drains much of

Superior vena cava

- runs from union of brachiocephalic veins behind manubrium to R. atrium

thorax

R. atrium of heart

Inferior vena cava - runs from junction

of

common

iliac

veins at L 5 to R. atrium of heart

L.

and

-

liver

R. hepatic veins

R. suprarenal (L.

suprarenal drains

into L. renal vein) L. and R. renal veins - kidneys

- adrenal glands

R. gonadal (L.

gonadal drains

Lumbar veins

into L. renal vein

- testis

(several pairs)

or ovary

-

posterior abdominal wall

FIGURE 19.24 Major veins of the systemic circulation, (a) Schematic flowchart. R.

-

common

pelvis

limb

Veins of R. lower limb (a)

and

iliac

R. lower

L.

-

common pelvis

iliac

and

L.

lower

imb

4

Veins of L. lower limb

Chapter 19

TABLE

19.9

1

The Cardiovascular System: Blood Vessels

759

(continued)

FIGURE 19.24 (continued) Major veins of the systemic circulation, (b) Illustration, anterior view. The vessels of the pulmonary circulation are not illustrated,

Dural sinuses

accounting for the incomplete

appearance of the

circulation

from the heart.

External jugular vein Vertebral vein

Subclavian vein

Internal jugular vein

Superior vena cava

Right and left brachiocephalic veins

Cephalic vein

Axillary vein

Brachial vein

Great cardiac vein

Basilic vein

Hepatic veins

Splenic vein

Hepatic portal vein

Median

cubital vein

Superior mesenteric vein Inferior

vena cava

Ulnar vein

Renal vein Inferior

mesenteric vein

Radial vein

Common External

vein

iliac iliac

vein

Internal iliac vein

Digital

veins

Femoral vein Great saphenous vein

Popliteal vein

Posterior

Anterior

tibial

tibial

vein

vein

Fibular vein

Dorsal venous arch

Dorsal veins (b)

digital

760

Maintenance of the Body

Unit IV

TABLE

19.1

22

Veins of the

Head and Neck

Most blood draining from the head and neck lected

by three pairs

is

the sphenoid body, receive venous blood from the ophthalmic veins of the orbits and the facial veins, which drain the nose and upper lip area. The internal carotid artery and cranial nerves III, IV, VI, and part of V all run through the cavernous sinus on their way to the or-

col-

of veins: the external jugular veins,

which empty into the subclavians, the internal jugular veins, and the vertebral veins, which drain into the brachiocephalic vein (see Figure 19.25a). Although most extracranial veins have the same names as the extracranial arteries, their courses and interconnections

bit

face.

Description and Area Drained

differ substantially.

Most veins

and

External jugular veins.

brain drain into the dural an interconnected series of enlarged chambers sinuses, located between the dura mater layers. The superior and inferior sagittal sinuses are in the falx cerebri, which dips down between the cerebral hemispheres. The inferior sagittal sinus drains into the straight sinus posteriorly (Figures 19.25a and c). The superior sagittal and straight sinuses then empty into the transverse sinuses, which run in shallow grooves on the internal surface of the occipital bone. These drain into the S-shaped sigmoid sinuses, which become the internal jugular veins as they leave the skull through the jugular foramen. The cavernous sinuses, which flank of the

Superior

Internal jugular veins.

sagittal sinus

jugular veins,

which

external

The

Facial

vein

Posterior auricular vein

Sigmoid sinus

Internal jugular vein

External jugular

Superior thyroid vein

vein

Middle thyroid vein

vein

Brachiocephalic veins

Subclavian vein

Superior vena cava (a)

brain,

paired internal

receive the bulk of blood

—

vein

flowchart.

left

draining from the brain, are the largest of the paired veins draining the head and neck. They arise from the dural venous sinuses, exit the skull via the jugular foramina, and then descend through the neck alongside the internal carotid arteries. As they move interiorly, they receive blood from some of the deep veins of the face and neck branches of the facial and superficial temporal veins (Figure 1 9.25b). At the base of the neck, each internal jugular vein joins the subclavian vein on its own side to form a brachiocephalic vein. As already noted, the two brachiocephalic veins unite to form the superior vena cava.

Occipital

Venous drainage of the head, neck, and

and

Vertebral veins. Unlike the vertebral arteries, the vertebral veins do not serve much of the brain. Instead they drain the cervical vertebrae, the spinal cord, and some small neck muscles. They run interiorly through the transverse foramina of the cervical vertebrae and join the brachiocephalic veins at the root of the neck.

Ophthalmic

FIGURE 19.25

right

served by the external carotid arteries. However, their tributaries anastomose frequently, and some of the superficial drainage from these regions enters the internal jugular veins as well. As the external jugular veins descend through the lateral neck, they pass obliquely over the sternocleidomastoid muscles and then empty into the subclavian veins.

vein

Vertebral

The

jugular veins drain superficial scalp and face structures

(a)

Schematic

Chapter 19

TABLE 19.10/

The Cardiovascular System: Blood Vessels

(continued)

Ophthalmic vein

Superficial

temporal vein Facial vein

Occipital vein

Posterior auricular vein

External jugular vein

Vertebral vein Internal

jugular vein

Superior and middle thyroid veins

Brachiocephalic

—

vein

Subclavian vein

Superior

vena cava

(b)

Superior sagittal sinus Falx cerebri Inferior sagittal

sinus Straight sinus

Cavernous sinus

Junction of sinuses

Transverse sinuses

Sigmoid sinus Jugular foramen

Right internal jugular vein

(c)

FIGURE 19.25 (continued) (b) Veins of

Venous drainage of the head, neck, and

the head and neck, right superficial aspect,

brain, right aspect.

(c)

brain.

Dural sinuses of the

761

762

Unit IV

TABLE 19

Maintenance of the Body

Veins of the Upper Limbs and Thorax

The deep veins of the upper limbs follow the paths of their companion arteries and have the same names (Figure 19.26a). However, except for the largest,

are paired veins that flank their artery.

The

most

superficial

veins of the upper limbs are larger than the deep veins

Subclavian

Internal

vein

jugular vein

External jugular vein

Brachiocephalic veins

Superior

vena cava

and are

easily seen just

beneath the skin. The median

cubital vein, crossing the anterior aspect of the elbow,

commonly used

samples or adminisintravenous medications. Blood draining from the mammary glands and the first two to three intercostal spaces enters the brachiocephalic veins. However, the vast majority of thoracic tissues and the thorax wall are drained by a complex network of veins called the azygos system (az'i-gos). The branching nature of the azygos system provides a collateral circulation for draining the abdominal wall and other areas served by the inferior vena cava, and there are numerous anastomoses between the azygos system and the inferior vena cava. is

to obtain blood

ter

Description and Areas Drained

Deep Veins of the Upper Limbs The most distal deep veins of the upper limb are the radial and ulnar veins. The deep and superficial palmar venous arches

of the

hand empty

into the radial and

ulnar veins of the forearm, which then unite to form the brachial vein of the arm. As the brachial vein enters the axilla,

it

becomes the

Accessory hemiazygos

becomes the subclavian vein

vein

Superficial Veins of the

axillary vein,

which

at the level of the first rib.

Upper Limbs

The superficial venous system begins with the dorsal venous arch (not illustrated), a plexus of superficial veins in the dorsum of the hand. In the distal forearm, this plexus drains into three major superficial veins the cephalic and basilic veins and the median antebrachial vein of the forearm which anastomose frequently as they course upward (see Figure 19.26b). The cephalic vein coils around the radius as it travels superiorly and then continues up the lateral superficial aspect of the arm to the shoulder, where it runs in the groove between the deltoid and pectoralis muscles to join the axillary vein. The basilic vein courses along the posteromedial aspect of the forearm, crosses the elbow, and then takes a deep course. In the axilla, it joins the brachial vein, forming the axillary vein. At the anterior aspect of the elbow, the median cubital vein connects the basilic and cephalic veins. The median antebrachial vein of the forearm lies between the radial and ulnar veins in the forearm and terminates (variably) at the elbow by entering either the basilic or the cephalic vein.

—

Azygos

Hemiazygos

vein

vein

-Posterior intercostal

veins

Cephalic

Median

Basilic

vein

antebrachial vein

vein

Intercostal

veins

-

—

The Azygos System Radialvein

-Ulnar vein

Deep palmar venous arch Metacarpal veins Superficial

palmar venous arch Digital

(a)

veins

The azygos system consists of the following vessels which flank the vertebral column laterally: Azygos vein. Located against the right side of the vertebral column, the azygos vein {azygos = unpaired) originates in the abdomen, from the right ascending lumbar vein that drains most of the right abdominal cavity wall and from the right posterior intercostal that drain the chest muscles. At the T 4 level, it arches over the great vessels that run to the right lung and empties into the superior

veins (except the

vena cava.

first)

Chapter 19

TABLE

19.1

The Cardiovascular System: Blood Vessels

continued)

Hemiazygos vein (he'me-a-zi'gus; "half the azygos"). This vessel ascends on the left side of the vertebral column. Its origin, from the left ascending lumbar vein and the lower (9th- 11th) posterior intercostal veins, mirrors that of the inferior portion of the azygos vein on the right. About midthorax, the hemiazygos vein passes in front of the vertebral column and joins the azygos vein.

Accessory hemiazygos vein. The accessory hemiazygos completes the venous drainage of the left (middle) thorax and can be thought of as a superior continuation of the hemiazygos vein. It receives blood from the 4th-8th posterior intercostal veins and then crosses to the right to empty into the azygos vein. Like the azygos, it receives venous blood from the lungs (bronchial veins).

Internal jugular vein

Brachiocephalic veins External jugular vein Right subclavian vein Left subclavian vein

Superior vena cava Axillary vein

Azygos vein Accessory hemiazygos vein Brachial vein

Cephalic vein

Hemiazygos vein

Basilic vein

Posterior intercostals

Inferior

Median

763

vena cava

cubital vein

Ascending lumbar vein

Median antebrachial vein

Cephalic vein

Radial vein

palmar venous arch

-Superficial

-Digital veins

(b)

FIGURE 19.26

Veins of the right upper limb and shoulder, (a) Schematic clarity, the abundant branching and anastomoses of these vessels are not shown. flowchart, (b) Illustration. For

— 764

Maintenance of the Body

Unit IV

TABLE 19.12

Veins of the

Abdomen needs. The hepatic portal system carries nutrient-rich blood from the digestive organs to the liver. As the blood percolates slowly through the liver sinusoids, hepatic parenchymal cells remove the nutri-

Blood draining from the abdominopelvic viscera and abdominal walls is returned to the heart by the inferior vena cava (Figure 19.27a). Most of its venous tributaries have names that correspond to the arteries serv-

tissue

ing the abdominal organs. Veins draining the digestive viscera empty into a common vessel, the hepatic portal vein, which transports this venous blood into the liver before it is allowed to enter the major systemic circulation via the hepatic veins (Figure 19.27b). Such a venous system is called a veins to capillaries (or sinusoids) to veins portal system and always serves very specific regional

ents they need for their various metabolic functions, and phagocytic cells lining the sinusoids rid the blood of bacteria and other foreign matter that has penetrated the digestive mucosa. The veins of the abdomen are listed in inferior to superior order.

Description and Areas Drained Lumbar veins. Several pairs of lumbar veins drain the posterior abdominal wall. They empty both directly

—

and into the ascending lumbar veins of the azygos system of the thorax. Gonadal (testicular or ovarian) veins. The right gonadal vein drains the ovary or testis on the right side of the body and empties into the inferior vena cava. The left member drains into the left renal vein superiorly.

into the inferior vena cava Inferior

vena cava Inferior

phrenic veins

Hepatic veins

Renal veins.

The

right

and

left

renal veins

drain the kidneys.

Hepatic

Suprarenal veins. The right suprarenal vein drains the adrenal gland on the right and empties into the inferior vena cava. The left suprarenal vein drains into the left renal vein.

—

portal

Hepatic portal vein

system

The short hepatic portal vein begins at the L 2 level. Numerous tributaries from the stomach and pancreas contribute to the hepatic portal system (Figure 19.27c), but the major vessels are as follows: Hepatic portal system.

uperior mesenteric vein

Splenic vein

Superior mesenteric vein: Drains the entire small intestine, part of the large intestine (ascending and transverse regions), and stomach. Splenic vein: Collects blood from the

stomach and pancreas, and then joins the superior mesenteric vein to form the hepatic portal vein. Inferior mesenteric vein: Drains the distal portions of the large intestine and rectum and joins the splenic vein just before that vessel unites with the superior mesenteric vein to form the hepatic portal vein. Hepatic veins. The right and left hepatic veins carry venous blood from the liver to the inferior vena cava. spleen, parts of the

Lumbar veins

R. ascending lumbar vein

Cystic veins. The cystic veins drain the bladder and join the hepatic veins.

gall-

Inferior phrenic veins. The inferior phrenic veins drain the inferior surface of the dia-

Common

iliac

phragm.

veins External

iliac

vein

Internal iliac veins (a)

-

Chapter 19

TABLE 19.12/

The Cardiovascular System: Blood Vessels

765

(continued)

Inferior

phrenic vein

Hepatic veins

Inferior

vena cava Left

suprarenal vein

Right

suprarenal vein

Renal veins

ascending lumbar vein Left

Right

Lumbar veins

gonadal vein

Left

gonadal vein

Common External

iliac

vein

iliac

vein

Internal iliac vein

(b)

Hepatic veins

Gastric veins Liver

Spleen

Inferior

vena cava

Hepatic portal vein Splenic vein

Right gastroepiploic vein

Inferior

mesenteric vein

Superior mesenteric vein

Small intestine

Large intestine

Rectum

FIGURE 19.27 Veins of the abdomen, (a) Schematic flowchart, (b) Tributaries of the inferior

vena

Venous drainage of abdominal organs not drained by the hepatic portal vein, (c) The cava.

(c)

hepatic portal circulation.

TABLE 19.13

Veins of the Pelvis and Lower Limbs

in the upper limbs, most deep veins of the lower limbs have the same names as the arteries they accompany and many are double. The two superficial saphenous veins (great and small) are poorly supported by surrounding tissues, and are common sites of varicosities. The great saphenous {saphenous = obvious) vein is frequently excised and used as a coronary bypass

As

Common

iliac

vein

Internal iliac vein

External

iliac

vein

vessel.

Description

Inguinal ligament

and Areas Drained

Deep

veins. After being formed by the union of the medial and lateral plantar veins, the posterior tibial vein ascends deep in the calf muscle (Figure 19.28) and

Femoral vein

receives the fibular (peroneal) vein. The anterior tibial vein, which is the superior continuation of the

Great saphenous vein (superficial)

dorsalis pedis vein of the foot, unites at the knee with

the posterior tibial vein to form the popliteal vein, which crosses the back of the knee. As the popliteal vein emerges from the knee, it becomes the femoral vein, which drains the deep structures of the thigh. The femoral vein becomes the external iliac vein as it enters the pelvis. In the pelvis, the external iliac vein unites with the internal iliac vein to form the

'Great

saphenous vein Popliteal

Popliteal

vein

vein

Internal iliac

Inferior

Anterior

vein

vena cava

tibial

vein

Fibular

(peroneal)

•Common

iliac

vein

Fibular

vein

(peroneal) •External

iliac

Small

vein

vein

saphenous vein Anterior tibial

(superficial)

vein

Posterior

Femoral Dorsalis

vein

tibial

vein

pedis vein

Small

Small

saphenous

saphenous

vein

vein

Plantar

Dorsal venous arch

veins

Metatarsal veins

Plantar arch

Digital

veins

Fibular

(peroneal)

(b)

vein Fibular

(peroneal) vein

common

iliac vein.

The

distribution of the internal

il-

iac veins parallels that of the internal iliac arteries. Plantar veins

Dorsal

venous

Deep

arch

plantar arch

Metatarsal

Digital

veins

veins Anterior

Posterior

(a)

FIGURE 19.28

Veins of the right lower limb. Schematic flowchart of anterior and posterior vessels. (b) Anterior view of the lower limb, (c) Posterior view of the leg and foot. (a)

Superficial veins. The great and small saphenous veins (sah-fe'nus) issue from the dorsal venous arch of the foot (Figure 19.28b and c). These veins anastomose frequently with each other and with the deep veins along their course. The great saphenous vein is the longest vein in the body. It travels superiorly along the medial aspect of the leg to the thigh, where it empties into the femoral vein just distal to the inguinal ligament. The small saphenous vein runs along the lateral aspect of the foot and then through the deep fascia of the calf muscles, which it drains. At the knee, it empties into the popliteal vein.

Chapter 19

767

The Cardiovascular System: Blood Vessels

Chapter Summary Media study below.

you additional help in Chapter 19 are referenced

tools that could provide

reviewing specific key topics of

B3I =

PART (pp.

2:

PHYSIOLOGY OF CIRCULATION

721-740)

Interactive Physiology.

Introduction to Blood Flow, Blood Pressure, and

PART 1: OVERVIEW OF BLOOD VESSEL STRUCTURE AND FUNCTION (pp. 712-721)

Resistance

Blood is transported throughout the body via a continuous system of blood vessels. Arteries transport blood away from the heart; veins carry blood back to the heart. Capillaries carry blood to tissue cells and are exchange sites.

sel,

1

.

(pp. 71 2-714)

Structure of Blood Vessel Walls

2. All blood vessels except capillaries have three layers: tunica interna, tunica media, and tunica externa. Capillary walls are composed of the tunica interna only.

Arterial

System

(pp.

expand and

recoil to

accommodate chang-

ing blood volume. Muscular (distributing) arteries carry blood to specific organs; they are less stretchy and more active in vasoconstriction. Arterioles regulate blood flow into capillary beds. 4.

Arteriosclerosis

is

a degenerative vascular disease. Initiit progresses through fatty

ated by endothelial lesions, streak, atherosclerotic,

Capillaries 5.

(pp.

and

arteriosclerotic stages.

of blood flowing through a ves-

entire circulation in a given period of

the force per unit area exerted on a is opposition to blood flow; blood viscosity and blood vessel length and diameter contribute to resistance. time. Blood pressure

is

2.

Blood flow

is

directly proportional to blood pressure

and

inversely proportional to resistance.

MTM

Cardiovascular System; Topic: Factors that Affect Blood Pressure, pages 1-15.

.

(pp.

722-724)

Systemic blood pressure is highest in the aorta and lowvenae cavae. The steepest drop in BP occurs in the

est in the

arterioles,

where resistance

2. Arterial

and on

is

greatest.

BP depends on compliance

how much

blood

is

of the elastic arteries

forced into them. Arterial blood

pressure is pulsatile, and peaks during systole,- this is measured as systolic pressure. During diastole, as blood is forced distally in the circulation by the rebound of elastic arteries, arterial BP drops to its lowest value, called the diastolic pressure.

minus diastolic pres(MAP) = diastolic pressure plus one-third of pulse pressure and is the pressure that keeps blood moving throughout the cardiac cycle. 3. Pulse pressure is systolic pressure

715-720)

Capillaries are microscopic vessels with very thin Most exhibit clefts, which aid in the exchange be-

walls.

tween the blood and

amount

the

an organ, or the

Systemic Blood Pressure

714-715)

Elastic (conducting) arteries are the large arteries close

to the heart that

is

721-722)

vessel wall by the contained blood. Resistance

1

3.

Blood flow

1.

(pp.

interstitial fluid.

Spider-shaped cells

sure.

The mean

arterial pressure

Low capillary pressure

called pericytes help to reinforce the external faces of

4.

capillaries.

delicate capillaries

6. The most permeable capillaries are sinusoids (wide, tortuous channels). Fenestrated capillaries with pores are next most permeable. Least permeable are continuous capillaries, which lack pores.

Vascular shunts (metarterioles-thoroughfare chanconnect the terminal arteriole and venule at opposite ends of a capillary bed. Most true capillaries arise from and rejoin the shunt channels. The amount of blood flowing into the true capillaries is regulated by precapillary

(40 to 15

mm Hg) protects the

from rupture while

still

allowing ade-

quate exchange across the capillary walls. 5.

Venous pressure

is

nonpulsatile and low (declining to

cumulative effects of resistance. Venous valves, large lumens, and functional adaptations (muscular and respiratory pumps) promote venous return. zero) because of the

7.

nels)

sphincters.

Maintaining Blood Pressure

(pp.

724-732)

1. Blood pressure varies directly with CO, peripheral resistance (R), and blood volume. Vessel diameter is the major factor determining resistance, and small changes in

vessel (chiefly arteriolar) diameter significantly affect blood

Venous System

(pp.

720-721)

Veins have comparatively larger lumens than arteries, and a system of valves prevents backflow of blood. Respiratory and skeletal muscle pumps aid return of venous blood 8.

to the heart. 9.

Normally most veins

are only partially filled with

blood; thus, they can serve as blood reservoirs.

Vascular Anastomoses

(p.

721)

10. The joining together of vessels to provide alternate channels for blood to reach the same organ is called an anastomosis. Vascular anastomoses also form between veins and

between

U\M

arterioles

and venules.

Cardiovascular System; Topic: Anatomy Review: Blood Vessel Structure and Function, pages 1-28.

pressure.

PfJ

Cardiovascular System; Topic: Measuring Blood Pressure, pages 1-13.

2. BP is regulated by autonomic neural reflexes involving baroreceptors or chemoreceptors, the vasomotor center (a sympathetic center that regulates blood vessel diameter), and vasomotor fibers, which act on vascular smooth muscle.

by falling BP (and to a lesser or falling blood pH or 0 2 blood C0 extent by a rise in 2/ center to increase vasoconvasomotor the stimulates levels) striction and the cardioacceleratory center to increase heart rate and contractility. Rising BP inhibits the vasomotor 3. Activation of the receptors

center (permitting vasodilation) and activates the cardioinhibitory center.

768

Maintenance of the Body

Unit IV

Higher brain centers (cerebrum and hypothalamus) neural controls of BP via medullary centers.

4.

vasodilation of arterioles serving the area and open the precapillary sphincters. Myogenic controls respond to changes

may modify

Bloodborne chemicals that increase BP by promoting vasoconstriction include epinephrine and NE (these also in5.

crease heart rate

and

contractility),

ADH,

angiotensin

Dynamics, pages 1-13.

and (generated in response to renin release by kidney PDGF and endothelin released by vascular endothelium cells.

The kidneys

directly regulate blood pressure

ing blood volume. Rising

by

regulat-

BP enhances filtrate formation and BP causes the kidneys to retain

fluid losses in urine; falling

water, increasing blood volume.

8. Indirect renal regulation of blood volume involves the renin-angiotensin mechanism, a hormonal mechanism. When BP falls, the kidneys release renin, which triggers the formation of angiotensin II (a vasoconstrictor) and release of aldosterone, which causes salt and water to be retained.

mim

Pulse and blood pressure measurements are used to as-

sess cardiovascular efficiency.

The

10. terial

pulse

is

the alternating expansion and recoil of ar-

walls with each heartbeat. Pulse points are also pres-

.

5. Nutrients, gases, and other solutes smaller than plasma proteins cross the capillary wall by diffusion. Water-soluble substances move through the clefts or fenestrations; fat-

soluble substances pass through the lipid portion of the endothelial cell membrane. 6. Fluid flows

occurring at capillary beds reflect the relative

outward (net hydrostatic pressure) forces minus the effect of inward (net osmotic pressure) forces. In general, fluid flows out of the capillary bed at the arterial end and effect of

reenters the capillary blood at the venule end.

Cardiovascular; Topic: Autoregulation and Capillary Dynamics, pages 14-38.

The small

net loss of fluid and protein into the interstispace is collected by lymphatic vessels and returned to the cardiovascular system. 7.

Circulatory shock occurs when blood perfusion of body is inadequate. Most cases of shock reflect low blood volume (hypovolemic shock), abnormal vasodilation (vascular shock), or pump failure (cardiogenic shock). 8.

tissues

Blood pressure

tory method.

of oxygen.

tial

sure points. 1 1

is controlled primarily by a drop and by myogenic mechanisms; and vasodilation of pulmonary circuit vessels occurs in response to high levels

pH

MIM

Cardiovascular System; Topic: Blood Pressure Regulation, pages 1—31.

9.

deficits

in

include atrial natriuretic peptide (also causes a decline in blood volume), nitric oxide released by the vascular endothelium, inflammatory chemicals, and alcohol.

more

most instances, autoregulation is controlled by oxygen and accumulation of local metabolites. However,

4. In

autoregulation in the brain

Chemicals that reduce BP by promoting vasodilation

7.

13 Cardiovascular; Topic: Autoregulation and Capillary

II

cells),

6.

in blood pressure.

is

routinely measured by the ausculta-

Normal blood

pressure in adults is 120/80 Hypotension is rarely a problem. Hyperthe major cause of myocardial infarct, stroke, and

(systolic/diastolic).

renal disease.

PART 3: CIRCULATORY PATHWAYS: BLOOD VESSELS OF THE BODY (pp. 740-741, 744-766)

BM Cardiovascular System; Topic: Measuring Blood

1.

tension

is

Pressure, pages 11, 12.

12. Hypotension, or low blood pressure (systolic pressure

below 100

mm Hg),

is

a sign of health in the well condi-

tioned. In other individuals

it

warns

of poor nutrition,

disease, or circulatory shock.

13. Chronic hypertension (high blood pressure) is persistent BP readings of 140/90 or higher. It indicates increased

peripheral resistance, which strains the heart and promotes vascular complications of other organs, particularly the eyes and kidneys. Risk factors are high-fat, high-salt diet, obesity,

member

advanced

age,

smoking,

of the black race or a family

stress,

with

and being

a

The pulmonary

circulation transports

-

laden blood to the lungs for oxygenation and carbon dioxide unloading. Blood returning to the right atrium of the heart is pumped by the right ventricle to the lungs via the pulmonary trunk. Blood issuing from the lungs is returned to the left atrium by the pulmonary veins. (See Table 19.3 and Figure 19.17.) 2.

The systemic

circulation transports oxygenated blood

all body tissues via the aorta and branches. Venous blood returning from the systemic circuit is delivered to the right atrium via the venae cavae.

from the

left

ventricle to

its

3. Tables 19.3 to 19.13

a history of

0 2 -poor, C0 2

and describe vessels

and Figures 19.18

to 19.28 illustrate

of the systemic circulation.

hypertension.

m\M

Developmantal Aspects of Blood Vessels (pp. 740-741)

Cardiovascular System; Topic: Measuring Blood Pressure, pages 11, 12.

Blood Flow Through Body Tissues: Tissue Perfusion (pp. 732-740)

1.

The

fetal

vasculature develops from embryonic blood is functioning in blood

and mesenchyme and delivery by the fourth week. islands

Blood flow is involved in delivering nutrients and wastes and from cells, gas exchange, absorbing nutrients, and forming urine.

2. Fetal circulation differs from circulation after birth. The pulmonary and hepatic shunts and special umbilical vessels

Blood flows fastest where the cross-sectional area of the vascular bed is least (aorta), and slowest where the crosssectional area is greatest (capillaries). The slow flow in capillaries allows time for nutrient-waste exchanges.

3. Blood pressure is low in infants and rises to adult values. Age-related vascular problems include varicose veins, hypertension, and atherosclerosis. Hypertension is the most important cause of sudden cardiovascular death in middle-aged men. Atherosclerosis is the most important cause of cardiovascular disease in the aged.

1.

to

2.

is the local adjustment of blood flow to individual organs based on their immediate requirements. is largely controlled by local chemical factors that cause

3. Autoregulation

It

are normally occluded shortly after birth.

Chapter 19

The Cardiovascular System: Blood Vessels

769

Review Questions Multiple Choice/Matching Select

Which statement does not accurately describe veins? They have less elastic tissue and smooth muscle than arteries, (b) they contain more fibrous tissue than arteries, (c) most veins in the extremities have valves, (d) they always 1.

(a)

Which

of the following tissues

is

(c)

collagenic tissue,

(d)

smootb muscle,

adipose tissue.

3. Peripheral resistance (a) is inversely related to the

increases,

(c) is

vascular bed,

Which

diam-

tends to increase if blood viscosity directly proportional to the length of the

eter of the arterioles,

(d) all

(b)

of these.

can lead to decreased venous (a) an increase in blood volume, (b) an increase in venous pressure, (c) damage to the venous valves, (d) increased muscular activity. 4.

of the following

return of blood to the heart?

(a)

blood pressure increases in response to: increasing stroke volume, (b) increasing heart rate,

(c)

arteriosclerosis, (d) rising blood

5. Arterial

Which

6.

volume,

(e) all

of these.

would nor result in the dilation and opening of the precapillary

of the following

of the feeder arterioles

0

sphincters in any capillary bed? (a) a decrease in 2 content of the blood, (b) an increase in 2 content of the blood, (c) a local increase in histamine, (d) a local increase in pH.

C0

The

structure of a capillary wall differs from that of a vein or an artery because (a) it has two tunics instead of 7.

smooth muscle, (c) it has a only the tunica interna, (d) none of these.

three, (b) there is less

tunic

—

single

baro receptors in the carotid and aortic bodies are sensitive to (a) a decrease in carbon dioxide, (b) changes in arterial pressure, (c) a decrease in oxygen, (d) all of these. 9. (a)

(d)

Short Answer Essay Questions 14. How is the anatomy of capillaries and capillary beds well suited to their function?

adaptations. 16. Write an equation showing the relationship between peripheral resistance, blood flow, and blood pressure.

Define blood pressure. Differentiate between systolic (b) What is the normal blood pressure value for a young adult? 17.

(a)

and

diastolic blood pressure,

18. Describe the neural

The myocardium receives its blood supply directly from the aorta, (b) the coronary arteries, (c) the coronary sinus, the pulmonary arteries.

steady despite the rhythmic pumping of the heart because of the (a) elasticity of the large arteries, (b) small diameter of capillaries, (c) thin walls of the veins, (d) venous valves.

20. How does the control of blood flow to the skin for the purpose of regulating body temperature differ from the control of nutrient blood flow to skin cells?

21. Describe neural and chemical (both systemic and local) on the blood vessels when one is fleeing from a mugger. (Be careful, this is more involved than it appears

effects exerted

at first glance.)

22. How are nutrients, wastes, and respiratory gases transported to and from the blood and tissue spaces?

23. (a) What blood vessels contribute to the formation of the hepatic portal circulation? (b) What is the function of (c)

from the heart to the right hand, we find that blood leaves the heart and passes through the aorta, the right subclavian artery, the axillary and brachial arteries, and through either the radial or ulnar artery to arrive at the hand. Which artery is missing from this sequence? (d)

right

(a)

coronary,

common

(b)

brachiocephalic,

(c)

cephalic,

24. Physiologists often consider capillaries and postcapillary (a) What functions do these vessels share? (b) Structurally, how do they differ?

12.

Which

rior

of the following

vena cava?

(a)

mesenteric vein,

lumbar (d)

do not drain directly into the veins,

(b)

renal veins.

hepatic veins,

(c)

in-

infe-

Thinking and

Clinical Application

Questions 1. Mrs. Johnson is brought to the emergency room after being involved in an auto accident. She is hemorrhaging and has a rapid, thready pulse, but her blood pressure is still

within normal limits. Describe the compensatory mechanisms that are acting to maintain her blood pressure in the face of blood loss.

A 60-year-old man is unable to walk more than 00 yards without experiencing severe pain in his left leg; the pain is relieved by resting for 5-10 minutes. He is told that the arteries of his leg are becoming occluded with fatty material and is advised to have the sympathetic nerves 1

ferior

a portal circulation a "strange"

venules together,

2.

carotid.

Why is

circulation?

is

11. Tracing the blood

for

19. Explain the reasons for the observed changes in blood flow velocity in the different regions of the circulation.

Critical 10. Blood flow in the capillaries

mechanisms responsible

controlling blood pressure.

this circulation?

The

8.

(a)

and

mainly responsible

for vasoconstriction? (a) elastic tissue, (b)

ens most?

15. Distinguish between elastic arteries, muscular arteries, arterioles relative to location, histology, and functional

carry deoxygenated blood. 2.

which layer of the vessel wall thicktunica media, (b) tunica interna, (c) tunica adventitia, (d) tunica externa. 13. In atherosclerosis,

(Some questions have more than one correct answer. the best answer or answers from the choices given.)

770

Unit IV

Maintenance of the Body

serving that body region severed. Explain how such surgery might help to relieve this man's problem. 3.

Your friend Joanie,

who knows

little

about science,

is

reading a magazine article about a patient who had an "aneurysm at the base of his brain that suddenly grew much larger." The surgeons' first goal was to "keep it from rupturing," and the second goal was to "relieve the pressure on the brain stem and cranial nerves." The surgeons were able to "replace the aneurysm with a section of plastic tubing," so the patient recovered. Joanie asks you what all this means. Explain. (Hint: Check this chapter's Related Clinical Terms.) 4.

The Agawam High School band

is

playing

some

lively

marches while the coaches are giving pep talks to their respective football squads. Although it is September, it is unseasonably hot (88°F) and the band uniforms are wool. Suddenly, Harry the tuba player becomes light-headed and faints. Explain his fainting in terms of vascular events.

5.

When

one

is

cold or the external temperature

is

low,

most venous blood returning from the distal part of the arm travels in the deep veins where it picks up heat (countercurrent mechanism) from the nearby brachial artery en route. However, when one is hot, and especially during exercise, venous return from the distal arm travels in the superficial veins and those veins tend to bulge superficially in a person who is working out. Explain why venous return takes a different route in the second situation.

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The Lymphatic System

Lymph Nodes

Lymphatic Vessels (pp. 1

.

772-774)

4.

distribution of lymphatic

functions of

and note

Describe the source of lymph of

lymph

Other Lymphoid Organs (pp. 777-779, 782) 5.

transport.

Lymphoid

Cells

and

lymph nodes.

their

and mechanism(s)

3.

Describe the general location, histological structure,

important functions.

(p.

776-777)

Describe the structure and vessels,

2.

(pp.

775)

and cellular population of lymphoid tissue, and name the major lymphoid organs.

and describe the other lymphoid organs of the body. Compare and contrast them with lymph nodes, structurally and functionally.

and Tissues

Describe the basic structure

Name

Developmental Aspects of the Lymphatic System (pp. 782-783) 6.

Outline lymphatic system development.

772

Unit IV

Maintenance of the Body

When

can't be we They tick off the names of the body's organ systems,

superstars!

all

mentally

the lymphatic flim-fat'ik) system

come

is

probably

mind. Yet without this quietly working system, our cardiovascular system would stop working and our immune system would be hopelessly impaired. The lymphatic system actually consists of two semi-independent parts: (1) a meandering network of lymphatic vessels and (2) various lymphoid tissues and organs scattered throughout the body. The lymphatic vessels transport back to the blood any fluids that have escaped from the blood vascular system. The lymphoid organs house phagocytic cells and lymphocytes, which play essential roles in the body is defense mechanisms and its resistance to disease. not the

first to

to

Lymphatic Vessels As blood

circulates through the body, nutrients,

wastes, and gases are exchanged between the blood

and the

interstitial fluid.

As explained

in Chapter 19,

the hydrostatic and colloid osmotic pressures operating at capillary beds force fluid out of the blood at the

We -now know

that they

owe

their permeability to

two unique structural modifications: 1.

The

endothelial cells forming the walls of lym-

phatic capillaries are not tightly joined; instead, the edges of adjacent cells overlap each other loosely,

forming easily opened,

flaplike minivalves (Figure

20.1b). 2. Collagen filaments anchor the endothelial cells to surrounding structures so that any increase in interstitial fluid volume opens the minivalves, rather than causing the lymphatic capillaries to collapse.

what we have is a system analogous to one-way swinging doors in the lymphatic capillary wall. When fluid pressure in the interstitial space is greater than the pressure in the lymphatic capillary, the minivalve flaps gape open, allowing fluid to enter the lymphatic capillary. However, when the pressure is greater inside the lymphatic capillary, the endothelial minivalve flaps are forced closed, preventing lymph from leaking back out as the pressure moves it along the vessel. Proteins in the interstitial space are unable to enter blood capillaries, but they enter lymphatic capSo,

illaries

easily.

In addition,

when

tissues are in-

ends of the beds ("upstream") and cause most of it to be reabsorbed at the venous ends ("downstream"). The fluid that remains behind in the tissue spaces, as much as 3 L daily, becomes part of the interstitial fluid. This leaked fluid, plus any plasma proteins that escape from the bloodstream, must be carried back to the blood to ensure that the cardiovascular system has sufficient blood volume to operate properly. This problem of circulatory dynamics is resolved by the lymphatic vessels, or lymphatics, an elaborate system of drainage vessels

permit uptake of even larger particles such as cell debris, pathogens (disease-causing microorganisms such as bacteria and viruses), and cancer cells. The pathogenic agents and cancer cells can then use the lymphatics to travel throughout the body. This threat to the body is partly resolved by the fact that the lymph takes "detours" through the lymph nodes, where it is cleansed of debris and "examined" by

that collect the excess protein-containing interstitial

lacteals (lak'te-alz) are present in the fingerlike

arterial

fluid

and return

to the bloodstream.

Once

intersti-

flamed, lymphatic capillaries develop openings that

cells of the

immune

system.

Highly specialized lymphatic capillaries called villi

The lymphatic vessels form a one-way system in which lymph flows only toward the heart. This

mucosa. The lymph draining from the digestive viscera is milky white [lacte = milk) rather than clear because the lacteals play a major role in absorbing digested fats from the intestine. This fatty lymph, called chyle ("juice"), is also delivered to the blood via the lymphatic stream. From the lymphatic capillaries, lymph flows through successively larger and thicker-walled channels first collecting vessels, then trunks, and

transport system begins in microscopic blind-ended

finally the largest of

lymphatic capillaries (Figure 20.1a), which weave between the tissue cells and blood capillaries in the

lymphatic collecting vessels have the same three tunics as veins, but the collecting vessels are thinnerwalled, have more internal valves, and anastomose more. In general these vessels in the skin travel along with superficial veins, and the deep lymphatic vessels of the trunk and digestive viscera travel with

tial fluid

it

enters the lymphatics,

it is

called

lymph

[lymph = clearwater).

Distribution and Structure of Lymphatic Vessels

loose connective tissues of the body.

Lymph

capillar-

widespread; however, they are absent from bones and teeth, bone marrow, and the entire central nervous system (where the excess tissue fluid drains into the cerebrospinal fluid). Although similar to blood capillaries, lymphatic capillaries are so remarkably permeable that they ies are

were once thought

to be

open

at

one end

like a straw.

of the intestinal

—

all,

the ducts (Figure 20.2).

The

the deep arteries.

The lymphatic trunks

are

of the largest collecting vessels,

areas of the body.

The major

formed by the union and drain fairly large

trunks,

named mostly

Chapter 20

from which they collect lymph, are the paired lumbar, bronchomediastinal, subclavian, and jugular trunks, and the single intestinal trunk for the regions

Venous

Arterial

system

system

eventually delivered to one of two large ducts in the thoracic region. The right lymphatic duct drains lymph from the right upper arm and the right side of the head and thorax (Figure 20.2a). The

much

is

duct receives lymph from the rest of the body. It arises anterior to the first two lumbar vertebrae as an enlarged sac, the cisterna chyli (sis-ter'nah ki'li), that collects lymph from the two large lumbar trunks that drain the lower limbs and from the intestinal trunk that drains the digestive organs. As the thoracic duct runs superiorly, it receives lymphatic drainage from the left side of the thorax, left upper limb, and the head region. Each terminal duct empties its lymph into the venous

773

-Lymph duct -Lymph trunk

(Figure 20.2b).

Lymph

The Lymphatic System

-Lymph node

Lymphatic system

>

Lymphatic

larger thoracic

collecting i

vessels, with valves

i.

p

/~ Lymphatic

Blood capillaries

circulation at the junction of the internal jugular

vein and subclavian vein on

its

own

side of the

Loose connective

body

tissue around

(Figure 20.2b).

-Venule

capillaries

Arteriole

•

HOMEOSTATIC IMBALANCE Like the larger blood vessels, the larger lymphatics receive their nutrient blood supply

from a branching

vasa vasorum. When lymphatic vessels are severely inflamed, the related vessels of the vasa vasorum become congested with blood. As a result, the pathway of the associated superficial lymphatics becomes visible through the skin as red lines that are tender to the touch. This unpleasant condition is called lymphangitis (lim"fan-ji'tis; angi = vessel). •

Lymph Transport Tissue

The lymphatic system lacks an organ that acts as a pump. Under normal conditions, lymphatic vessels are low-pressure conduits, and the same mechanisms that promote venous return in blood vessels act here as well the milking action of active skeletal muscles, pressure changes in the thorax during breathing, and valves to prevent backflow. Lymphatics are usually bundled together in connective tissue sheaths along with blood vessels, and pulsations of nearby arteries also promote lymph flow. In addition to these mechanisms, smooth muscle in the walls of the lymphatic trunks and thoracic duct contracts

Tissue

cell

(a)

—

FIGURE

to

connective tissue

Endothelial cell

Flaplike

20.1

Distribution and special structural

features of lymphatic capillaries, relationship

between

a capillary

system and lymphatic of fluid

Filaments -

anchored

movement,

(b)

bed

capillary overlap

(a) Structural

of the blood vascular

Arrows indicate direction Lymphatic capillaries begin as blind-

capillaries.

ended tubes. Adjacent endothelial

cells in a

each other, forming

minivalve

Fibroblast in loose connective tissue

lymphatic

flaplike minivalves.

(b)

Blood

Lymphatic

capillaries

capillary

fluid

774

Unit IV

Maintenance of the Body

Left jugular

Right jugular trunk

trunk

Right lymphatic duct

Internal

jugular veins

Right subclavian trunk

Left subclavian

Right subclavian vein

trunk

Right bronchomediastinal

Left subclavian

trunk

vein

Brachiocephalic veins

mediastinal

Left

broncho-

trunk

Superior vena cava

Entrance

Azygos vein

thoracic duct

Cisterna chyli

subclavian vein

of

into left

Right lumbar trunk

Esophagus Trachea Ribs

Regional

Entrance

lymph nodes

right

of

Thoracic duct

lymphatic

duct into right subclavian vein

Hemiazygos vein

Cervical

nodes Internal

jugular vein

Entrance

of

thoracic

duct into left subclavian vein

Axillary

nodes

lumbar

Thoracic duct

Left

Aorta

trunk Inferior

Cisterna chyli

vena cava

Intestinal trunk

Lymphatic collecting

vessels

FIGURE 20.2

The lymphatic system,

(a)

General

distribution of lymphatic collecting vessels

and regional

lymph nodes. The area tinted pale green

drained by the

right

lymphatic duct; the rest of the body

is

(tan)

is

drained by

the thoracic duct, (b) Major veins'in the superior thorax

showing entry points of the thoracic and right lymphatic ducts. The major lymphatic trunks are also identified.

(a)

rhythmically, helping to

pump

the

lymph

along.

Even so, lymph transport is sporadic and slow. About 3 L of lymph enters the bloodstream every 24 hours, a volume almost exactly equal to the amount of fluid lost to the tissue spaces from the bloodstream in the same time period. Movement of extremely important in propelling lymph through the lymphatics. When physical adjacent tissues

is

activity or passive

much more

increase,

lymph flows

rapidly (balancing the greater rate of

from the blood in such situations). Hence, a good idea to immobilize a badly infected body

fluid loss it is

movements

part to hinder flow of inflammatory material from

that region.

,

^J(l%

homeostatic imbalance

Anything that prevents the normal return of lymph to the blood, such as blockage of the lymphatics by tumors or removal of lymphatics during cancer surgery, results in short-term but severe localized

edema (lymphedema). However, lymphatic is

drainage

eventually reestablished by regrowth from the vesremaining in the area. •

sels

—T )

.

Chapter 20

Lymphoid

Cells

How

and Tissues

The Lymphatic System

775

reticular connective tissue classified?

is

In order to understand the basic aspects of the

lymphatic system's role in the body, we investigate lymphoid the components of lymphoid organs cells and lymphoid tissues before considering the organs themselves.

—

—

Lymphoid

Macrophage

Cells Reticular cells

Infectious microorganisms that

manage

to penetrate

on

the underlying loose connective tissues. These invaders are fought off by the inflammatory response, by phagocytes (macrophages), and by lymphocytes. Lymphocytes, the main warriors of the immune system, arise in red bone marrow (along with other

Lymphocytes

Medullary sinus

formed elements). They then mature into one of the two main varieties of immunocompetent cells cells (T lymphocytes) or B cells (B lymphocytes) that protect the body against antigens. [Antigens are anything the body perceives as foreign, such as bacteria and their toxins, viruses, mismatched RBCs, or

Reticular

—

cancer cells.) Activated T cells manage the immune response and some of them directly attack and destroy foreign cells. B cells protect the body by producing plasma cells, daughter cells that secrete antibodies into the blood (or other body fluids). Antibodies immobilize antigens until they can be destroyed by phagocytes or other means. The precise roles of the lymphocytes in immunity are explored in Chapter 2 1 Lymphoid macrophages play a crucial role in body protection and in the immune response by phagocytizing foreign substances and by helping to activate T cells. So, too, do the spiny-looking dendritic cells found in lymphoid tissue. Last but not least are the reticular cells, fibroblastlike cells that produce the reticular fiber stroma (stro'mah), which is the network that supports the other cell types in the lymphoid organs (Figure 20.3).

Lymphoid Tissue Lymphoid (lymphatic) tissue is an important component of the immune system, mainly because it 1 houses and provides a proliferation site for lymphocytes and (2) furnishes an ideal surveillance vantage point for lymphocytes and macrophages. Lymphoid (

tissue, largely

composed

of a type of loose connective

connective tissue, dominates lymphoid organs except the thymus. Macrophages live on the fibers of the reticular network, and in the spaces of the network are huge numbers of lymphocytes that have squeezed through tissue called reticular all

the

reticular

fibers

the body's epithelial barriers quickly proliferate in

fiber

FIGURE 20.3 Reticular tissue in a human lymph node. Scanning electron micrograph (1 100X).

lymphoid tissue (Figure 20.3), and then leave body again. The cycling of lymphocytes between the circulatory vessels, lymphoid tissues, and loose connective tissues of the body ensures that lymphocytes reach infected or damaged sites quickly. in the

to patrol the

Lymphoid

tissue

comes

in various "packages."

Diffuse lymphatic tissue, consisting of a few scattered reticular tissue elements, is found in virtually every body organ, but larger collections appear in the lamina propria of mucous membranes and in lymphoid organs. Lymphoid follicles (nodules) represent another way lymphoid tissue is organized. Like diffuse lymphatic tissue, they lack a capsule, but follicles are solid, spherical bodies consisting of tightly packed reticular elements and cells. Follicles often have lighter- staining centers, called germinal

B cells predomand these centers enlarge dramatically when the B cells are dividing rapidly and producing plasma cells. In many cases, the follicles are found forming part of larger lymphoid organs, such as lymph nodes. However, isolated aggregations centers. Follicular dendritic cells and inate in germinal centers,

of

lymphatic

follicles

occur in the intestinal wall as

Peyer's patches and in the appendix.

the walls of postcapillary venules coursing through this

tissue.

The lymphocytes

reside temporarily

'jadojd anss/; SA/;oauuco asoo7

776

Maintenance of the Body

Unit IV

What

is

the benefit of having fewer efferent than

afferent lymphatics

in

lymph nodes?

Trabecula

Germinal center

in

follicle

Subcapsular

Follicles

sinus

Trabecula

Afferent

lymphatic vessels

Subcapsular sinus

Capsule

Medullary cords Medullary cord

Efferent

Medullary sinuses

lymphatic vessels

Medullary sinus

(b)

(a)

FIGURE 20.4 (a)

Lymph node.

Longitudinal view of the internal

structure of a

on whereas fewer efferent lymphatics exit at its hilus. Arrows indicate the direction of lymph flow

several afferent lymphatics converge

lymph node and

associated lymphatics. Notice that

its

convex

Lymph Nodes

nodes. There are hundreds of these small organs, but because they are usually embedded in connective tissue, they are not ordinarily seen. Large clusters of

lymph nodes occur near the body and

node

effectively preventing

The principal lymphoid organs in the body are the lymph nodes, which cluster along the lymphatic vessels of the body. As lymph is transported back to the bloodstream, it is filtered through the lymph

cervical regions, places

trunks (see Figure 20.2a).

Lymph nodes have two

(60x).

them from being

delivered to

the blood and spreading to other parts of the body. (2) They help activate the immune system. Lymphocytes, also strategically located in the

lymph nodes,

monitor the lymphatic stream for the presence of antigens and mount an attack against them. Let's look at how the structure of a lymph node supports these defensive functions.

surface in the in-

where the lymphatic collecting vessels converge to form

guinal, axillary,

and out of the node, (b) Photomicrograph of part of a lymph into

side,

Structure of a Lymph nodes

Lymph Node

vary in shape and

size,

but most are

bean shaped and less than 2.5 cm 1 inch) in length. Each node is surrounded by a dense fibrous capsule from which connective tissue strands called trabeculae extend inward to divide the node into a number of compartments (Figure 20.4). The node's internal framework or stroma of reticular fibers (

basic functions, both

concerned with body protection. (1) They act as lymph "filters." Macrophages in the nodes remove and destroy microorganisms and other debris that enter the lymph from the loose connective tissues,

physically supports the ever-changing population of

lymphocytes.

A I Buisueap i/diuA/ ui

aiejnuunDDe oj

sj/

u,da//fy

io\ siu/; sjouj 6u//wo//e 'sspou

sasneo s;uaja^a j9M9}

BuiAej-j

lymph node has two

gions, the cortex

histologically distinct re-

and the medulla. The

superficial

Chapter 20

The Lymphatic System

777

part of the cortex contains densely packed follicles,

many with

germinal centers heavy with dividing B cells. Dendritic cells nearly encapsulate the follicles and abut the deeper part of the cortex, which primarily houses T cells in transit. The T cells circulate continuously between the blood, lymph nodes, and lymph, performing their surveillance role. Medullary cords, which are thin inward extensions from the cortical lymphoid tissue, contain both types of lymphocytes plus plasma cells and they define the medulla. Throughout the node are lymph

lymph

Tonsils region)

Thymus thorax;

(in

most

active during

youth)

spanned by crisscrossing reticular fibers. Numerous macrophages reside on these reticular fibers and phagocytize foreign matter in the lymph as it flows by in the sinuses. Additionally, some of the lymph-borne antigens in the sinuses, large

(in

pharyngeal

capillaries

Spleen (curves around lett side of stomach)

lymph leak into the surrounding lymphoid tissue, where they activate lymphocytes to mount an immune attack against them.

percolating

Peyer's patches (in intestine)

Appendix

Circulation

Lymph

in

the Lymph Nodes

enters the convex side of a

lymph node

through a number of afferent lymphatic vessels. It then moves through a large, baglike sinus, the subcapsular sinus, into a number of smaller sinuses that cut through the cortex and enter the medulla. The lymph meanders through these sinuses and finally exits the node at its hilus (hi'lus), the indented region on the concave side, via efferent lymphatic vessels. Because there are fewer efferent vessels draining the node than afferent vessels feeding it, the flow of lymph through the node stagnates somewhat, allowing time for the lymphocytes and macrophages to carry out their protective functions. Lymph passes through several nodes before it is completely cleansed.

FIGURE 20.5 and

Lymphoid organs.

Sometimes lymph nodes

are

Lymph nodes of

agents they are trying to destroy. For example,

when

numbers of bacteria are trapped in the nodes, nodes become inflamed, swollen, and tender to

large

the

the touch, a condition often referred to (erroneously)

Such infected lymph nodes are buboes (bu'boz). (Buboes are the most obvious symptom of bubonic plague, the "Black Death" that killed much of Europe's population in the late Middle Ages.) Lymph nodes can also become secondary cancer sites, particularly in metastasizing cancers that enter lymphatic vessels and become as swollen glands.

called

trapped there.

The

fact that cancer-infiltrated

lymph

nodes are swollen but not painful helps distinguish cancerous lymph nodes from those infected by microorganisms. •

are just

one example

lymphoid organs or aggregates

of the

of

tonsils,

and Peyer's patches

many types

lymphatic tissue

in the body. Others are the spleen,

thymus

gland,

of the intestine (Figure

20.5), as well as bits of lymphatic tissue scattered in

the connective tissues.

posed of

overwhelmed by the

thymus,

Other Lymphoid Organs

The common

feature of

all

makeup: All are comreticular connective tissue. Although all

these organs

"^J^ HOMEOSTATIC IMBALANCE

Tonsils, spleen,

Peyer's patches.

is

their tissue

lymphoid organs help protect the body, only the lymph nodes filter lymph. The other lymphoid organs and tissues typically have efferent lymphatics draining them, but lack afferent lymphatics.

Spleen The

blood-rich spleen is about the size of a fist the largest lymphoid organ. Located in the left side of the abdominal cavity just beneath the diaphragm, it curls around the anterior aspect of the stomach (Figures 20.5 and 20.6). It is served by the large splenic artery and vein, which enter and exit

and

soft,

is

on

concave anterior surface. site for lymphocyte prolifsurveillance and response. But eration and immune perhaps even more important are its blood-cleansing functions. Besides extracting aged and defective the hilus

The

its slightly

spleen provides a

778

Maintenance of the Body

Unit IV

FIGURE 20.6

The spleen, (a) Gross structure, (b) Diagram of the histological Photograph of the spleen in its normal position in the abdominal anterior view, (d) Photomicrograph of spleen tissue showing white and red

structure, (c) cavity,

pulp regions (30x).

cells and platelets from the blood, its macrophages remove debris and foreign matter from blood flowing through its sinuses. The spleen also performs three additional, and related, functions.

blood

1.

stores

It

blood

some

of the

cells for later

iron for

breakdown products

reuse

(for

making hemoglobin) and

the blood for processing by the 2. (a

It is

example,

it

of red

salvages

releases others to

liver.

a site of erythrocyte production in the fetus

capability that normally ceases after birth).

3. It stores

blood platelets.

lymph nodes,

surrounded by a fibrous capsule, has trabeculae that extend inward, and contains both lymphocytes and macrophages. Consistent with its blood-processing functions, it Like

the spleen

is

huge numbers of erythrocytes. Areas of lymphocytes suspended on reticular fibers are called white pulp. The white pulp clusters or forms "cuffs" around the central arteries (small branches of the splenic artery) in the organ and forms what appear to be islands in a sea of red pulp. Red pulp is essentially all remaining splenic tissue, that is, the venous sinuses (blood sinusoids) and the splenic cords, regions of reticular also contains

composed mostly

connective tissue exceptionally rich in macrophages. Red pulp is most concerned with disposing of wornout red blood cells and bloodborne pathogens, whereas white pulp is involved with the immune functions of the spleen. The naming of the pulp regions reflects their appearance in fresh spleen tissue rather than their staining properties. Indeed, as can

-

Chapter 20

779

The Lymphatic System

Thymic lobule

Hassall's

corpuscle

FIGURE 20.7 shows

its

The thymus. The photomicrograph

be seen in the photomicrograph in Figure 20. 6d, the white pulp takes on a purplish hue and sometimes appears darker than the red pulp.

Because the spleen's capsule

relatively thin, a diit

to rupture,

Under such conditions the spleen must be removed quickly (a procedure called a splenectomy) and the splenic artery tied off to prevent life-threatening hemorrhage and shock. Surgical removal of the spleen seems to create few problems because the liver and bone marrow take over most of its functions. In children younger than 1 2, the spleen will regenerate if a small in the body.

•

Thymus The

bilobed

thymus

histology,

to a cauliflower

it

head

helps to com-

— the flowerets

represent thymic lobules, each containing an outer

but a few macrophages are scattered is

blow or severe infection may cause

it is left

thymus

the rapidly dividing lymphocytes are densely packed,

spilling blood into the peritoneal cavity.

part of

To understand thymic pare the

cortex and an inner medulla (Figure 20.7). Most thymic cells are lymphocytes. In the cortical regions

HOMEOSTATIC IMBALANCE rect

thymus

of a portion of the

lobules with cortical and medullaiy regions (20x).

(thi'mus) has important func-

tions primarily during the early years of life. It is found in the inferior neck and extends into the superior thorax, where it partially overlies the heart deep

sternum (see Figures 20.5 and 20.7). By secreting the hormones thymosin and thymopoietin, the thymus causes T lymphocytes to become immunocompetent; that is, it enables them to function

The

among them.

lighter-staining medullary areas contain fewer

lymphocytes plus some bizarre structures called Hassall's or thymic corpuscles. Hassall's corpuscles

appear to be areas of degenerating cells, but their significance is unknown. Because the thymus lacks B cells, it has no follicles. The thymus differs from other lymphoid organs in two other important ways. First, it functions strictly in T lymphocyte maturation and thus is the only lymphoid organ that does not directly fight antigens. In fact, the so-called blood-thymus barrier keeps bloodborne antigens horn leaking into the cortical regions to prevent premature activation of the immature lymphocytes. Second, the stroma of the thymus consists of epithelial cells rather than reticular fibers. These

thymocytes secrete the hormones that stimulate the lymphocytes to become immunocompetent.

to the

against specific pathogens in the

immune

response.

Prominent in newborns, the thymus continues to increase in size during childhood, when it is most active. During adolescence its growth stops, and it starts to atrophy gradually. By old age it has been replaced almost entirely by fibrous and fatty tissue and is difficult to distinguish from surrounding connective tissue.

Tonsils lymphoid organs. They form a ring of lymphatic tissue around the entrance to the pharynx (throat), where they appear as swellings

The

tonsils are the simplest

of the

mucosa

(Figure 20.5).

according to location.

The

The

tonsils are

named

paired palatine tonsils are

located on either side at the posterior end of the oral cavity. These are the largest of the tonsils and the

ones most often infected. The lingual tonsils, paired

lumpy

collections of

lymphoid

follicles, lie at

the base

MAKING CONNECTIONS

SYSTEM CONNECTIONS: Homeostatic

Interrelationships

Between the

Lymphatic System/Immunity and Other Body Systems Nervous System Lymphatic vessels pick up leaked plasma proteins

in

PNS

structures;

immune

cells

fluid

and

protect

PNS structures from specific pathogens The nervous system innervates larger lymphatics; immune functions; immune response

opiate neuropeptides influence the brain helps regulate

Endocrine System

Lymphatic vessels pick up leaked fluids and prolymph distributes hormones; immune cells protect endocrine organs

teins;

The thymus produces hormones that promote development of lymphatic organs and "program" T cells; stress hormones depress immune activity Cardiovascular System

Lymphatic vessels pick up leaked plasma and

removes and destroys aged RBCs and debris; stores iron and platelets; immune cells protect cardiovascular organs from specific pathogens Blood is the source of lymph; lymphatics develop from veins; blood circulates immune elements proteins; spleen

Respiratory System

Lymphatic vessels pick up leaked fluids and proteins from respiratory organs; immune cells protect respiratory organs from specific pathogens; the tonsils

and plasma Integumentary System Lymphatic vessels pick up leaked plasma fluid and proteins from the dermis; lymphocytes in lymph enhance the skin's protective role by defending against specific pathogens via the

The ical

skin's keratinized

immune response

epithelium provides a mechan-

barrier to pathogens; Langerhans' cells

and

dermal macrophages act as antigen presenters the

immune

inhibits

Skeletal

response; acid

pH

in

of skin secretions

growth of bacteria on the

skin

secrete the antibody IgA) prevent pathogen invasion The lungs provide 0 2 needed by lymphoid/immune cells and eliminate CO2; the pharynx houses the tonsils; respiratory "pump" aids lymph flow

Digestive System

Lymphatic vessels pick up leaked fluids and proteins from digestive organs; lymph transports some products of fat digestion to the blood; lymphoid follicles in

the intestinal wall prevent invasion of pathogens

pathogens' entry into blood

inhibits

Lymphatic vessels pick up leaked plasma

immune

the respiratory mucosa (which

The digestive system digests and absorbs nutrients needed by cells of lymphoid organs; gastric acidity

System

proteins from the periostea;

cells in

cells

fluid

and

protect

bones from pathogens The bones house hematopoietic tissue which produces the lymphocytes (and macrophages) that populate lymphoid organs and provide immunity

Urinary System

Lymphatic vessels pick up leaked fluid and proteins from urinary organs; immune cells protect urinary

organs from specific pathogens Urinary system eliminates wastes

and maintains ho-

meostatic water/acid-base/electrolyte balance of the

Muscular System

blood

Lymphatic vessels pick up leaked fluids and proteins; immune cells protect muscles from skeletal

for

lymphoid/immune

some pathogens

cell

functioning; urine

out of the body

Reproductive System

pathogens

The

flushes

muscle "pump" aids the flow of

lymph; heat produced during muscle initiates feverlike effects

activity

fluid and proteins; pathogens immune cells protect against Reproductive organs' hormones may influence

Lymphatic vessels pick up leaked

immune

functioning; acidity of vaginal secretions

bacteriostatic

is

CLOSER

THE LYMPHATIC SYSTEM: Immunity and

CONNECTIONS

Cardiovascular System

body

cells are bathed by lymph. Nonetheless, system with its ghostly vessels and wellthe lymphatic hidden (for the most part) organs and tissues is elusive All living

ground mole that tunnels it's there, but you never see it as it quietly goes about its business. Since hormones made by endocrine organs are released into the extracellular space, and lymphatic vessels take up the fluid containing them, there is little question that lymph is an important medium for delivering hormones throughout the body. Lymph plays a similar delivery role as it delivers fats absorbed by the digestive organs. Our immune system, charged with protecting the body from specific pathogens, is often considered a separate and independent functional system. However, it is impossible to divorce the immune system from the lymphatic system because lymphoid organs are the programming sites and seedbeds for the immune cells and provide crucial vantage points for monitoring blood and lymph for the presence of foreign substances. Less understood are the intimate interactions between the immune cells that populate the lymphoid tissues and the nervous and endocrine and hard to pin down.

Like a

throughout your yard, you know

systems, but this interesting topic

Chapter

21 to give

immune system

in

is

is

you the opportunity to consider the detail.

its

chief "master"

this relationship that

is

we

the cardiovascular system. will

—

we eat and drink lost water is replaceable few minutes, right? The answer, of course, is "true." But what would still be missing is the leaked proteins, and these plasma proteins (most made by the liver) take time and energy to make. Since plasma proteins play a major role in keeping fluid in blood vessels (or encouraging its return), without them our blood vessels would contain too little fluid to support blood circulation. And without blood circulation, the whole body would die for lack of oxygen and nutrients and drown in its own wastes. Lymphoid organs also help to maintain the health and purity of bloodlymph nodes filter microorganisms and other debris from lymph before it is allowed to reenter the blood, and the spleen performs the same cleansing service for everything in a

blood.

addition, the spleen disposes of inefficient,

In

deformed, or aged erythrocytes. However, this relationship is not entirely one-way. Lymphatic vessels spring from veins of the cardiovascular system, and blood delivers oxygen and nutrients to all body organs, including lymphoid ones. Blood also provides a means for (1) rapid transport of lymphocytes

(immune

cells)

that continuously patrol the

foreign substances and

deferred to

Although the lymphatic system serves the entire body,

Interrelationships with the

It

explore further here.

body

for

broad distribution of antibodies (made by B cells and plasma cells), which bind to foreign substances and immobilize them until they can be disposed of by phagocytosis or other means. (2)

Furthermore, the endothelial

express

cells of capillaries

surface protein "signals" (integrins/adhesion molecules) that lymphocytes can recognize

when the surrounding

Cardiovascular System

area

By now you are probably fairly comfortable with the fact that the lymphatic system picks up and returns leaked fluid and proteins to the blood vascular system.

the sites where their protective serneeded, and the extremely porous walls of the postcapillary venules allow them to slip through the

So, what's the big deal?

We

ingest water

in virtually

is

injured or infected. Hence, capillaries guide

immune

cells to

vices are

vessel wall to get there.

CLINICAL

CONNECTIONS Lymphatic System/Immunity

Relative to these observations: 1.

Case study: Back to following the progress of Mr. Hutchinson, we learn that the routine complete blood count (CBC) performed on admission revealed that his leukocyte count is dangerously low and followup lab tests show that his lymphocytes are deficient. One day postsurgery, he complains of pain in his right ring finger (that hand had a crush injury). When examined, it was noted that the affected finger and the dorsum of the right hand were edematous, and red streaks radiated superiorly on his right forearm. Higher than normal doses of antibiotics are prescribed, and a applied to the affected arm. Nurses are instructed to apply gloves and gown when giving Mr. Hutchinson his care.

sling

is

What do

the red streaks emanating from the

bruised finger indicate?

What would you conclude

problem was if there were no red streaks but the arm was very edematous? 2.

Why

is

it

important that Mr. Hutchinson not

the affected arm excessively

(i.e.,

why was the

his

right

move sling

ordered)?

How

might the low lymphocyte count, megadoses of antibiotics, and orders for additional clinical staff 3.

protection be related?

Do you predict that Mr. Hutchinson's recovery be uneventful or problematic? Why?

4.

(Answers

in

will

Appendix

F)

in the posterior wall of the

strategy produces a wide variety of immune cells that have a "memory" for the trapped pathogens. Thus,

nasopharynx. The tiny tubal tonsils surround the openings of the auditory tubes into the pharynx. The tonsils gather and remove many of the pathogens en-

the body takes a calculated risk early on (during childhood) for the benefits of heightened immunity and better health later.

of the tongue.

The pharyngeal

the adenoids

enlarged)

if

is

tonsil (referred to as

pharynx in food or in inhaled air. The lymphoid tissue of the tonsils contains follicles with obvious germinal centers surrounded by diftering the

fusely scattered lymphocytes.

The

tonsils are not

and the epithelium overlying them invaginates deep into their interior, forming

fully encapsulated,

The

Aggregates of Lymphoid

Follicles

Peyer's patches (pi'erz) are large isolated clusters of

lymphoid

follicles,

structurally similar to the tonsils,

that are located in the wall of the distal portion of the

and particulate matter, and the bacteria work their way through the mucosal epithelium into the lymphoid tissue, where most are destroyed. It seems

small intestine (Figures 20.5 and 20.9). Lymphoid follicles are also heavily concentrated in the wall of the appendix, a tubular offshoot of the first part of the large intestine. Peyer's patches and the appendix

a bit dangerous to "invite" infection this way, but this

are in

blind-ended crypts (Figure 20.8).

crypts trap bac-

teria

an

ideal position

(

1

)

to destroy bacteria (which

are present in large numbers in the intestine), thereby preventing these pathogens from breaching the intestinal wall, and (2) to generate many "memory" lymphocytes for long-term immunity. Peyer's patches, all located in the dithe appendix, and the tonsils gestive tract

— and lymphoid

—

follicles in

the bronchi (organs of the respiratory

the collection of small lymphoid

the walls of

tract), are

part of

tissues referred to as

mucosa-associated lymphatic tissue (MALT). Collectively, MALT protects the digestive and respiratory tracts from the never-ending onslaughts of foreign matter entering those cavities.

Developmental Aspects of the Lymphatic System FIGURE 20.9

Peyer's patches. Histological structure of

aggregated lymphoid

follicles

— Peyer's patches —

wall of the ileum of the small intestine

(20x).

(P)

in

the

(SM = submucosa)

By the

week

embryonic development, the beginnings of the lymphatic vessels and the main clusters of lymph nodes are apparent. These arise from fifth

of

The

first

lymph

sacs from developing veins. of these, the jugular lymph sacs, arise at the

the budding of

junctions of the internal jugular and subclavian veins and form a branching system of lymphatic vessels throughout the thorax, upper extremities, and head. The two main connections of the jugular

lymph sacs to the venous system are retained and become the right lymphatic duct and, on the left, the

783

The Lymphatic System

Chapter 20

sues elsewhere in the embryo's body. Except for the spleen and tonsils, the lymphoid organs are poorly developed before birth. Shortly after birth, they become heavily populated by lymphocytes, and their

development

parallels the maturation of the imsystem. There is some evidence that the embryonic thymus produces hormones that control the development of the other lymphoid organs.

mune

superior part of the thoracic duct. Caudally the elab-

abdominal lymphatics buds largely from the primitive inferior vena cava. The lymphatics of the pelvic region and lower extremities form from sacs on the iliac veins. Except for the thymus, which is an endodermal derivative, the lymphoid organs develop from mesodermal mesenchymal cells that migrate to particular body sites and develop into reticular tissue. The thymus, the first lymphoid organ to appear, forms as an outgrowth of the lining of the primitive pharynx. It then detaches and migrates caudally to the thorax where it becomes infiltrated with immature lymphocytes derived from hematopoietic tis-

*

orate system of

Although the functions of the lymphatic vessels and lymphoid organs overlap, each helps maintain body homeostasis in unique ways, as summarized in Making Connections. The lymphatic vessels help maintain blood volume. The macrophages of lymphoid organs remove and destroy foreign matter in lymph and blood. Additionally, lymphoid organs and tissues provide sites from which the immune system can be mobilized. In Chapter 21, we continue this story as we examine the inflammatory and immune responses that allow us to resist a constant barrage of pathogens.

Related Clinical Terms Elephantiasis (el"le-fan-ti'ah-sis) Typically a tropical disease in which the lymphatics (particularly those of the male's lower limbs and scrotum) become clogged with parasitic roundworms, an infectious condition called filariasis; swelling (due to edema) reaches enormous proportions.

Hodgkin's disease

A malignancy of the

symptoms include

swollen, nonpainful

lymph nodes; lymph nodes, fa-

and often persistent fever and night sweats. Characby presence of giant cells of uncertain origin called Reed-Sternberg cells. Etiology unknown,- treated with radiatigue,

terized

tion therapy; high cure rate.

Lymphadenopathy pathy = disease)

(lim-fad"e-nop'ah-the adeno

Any

;

disease of the

=

a gland;

lymph nodes.

Lymphangiography (lim-fan"je-og'rah-fe) Diagnostic procedure in which the lymphatic vessels are injected with radiopaque dye and then visualized with X rays.

Lymphoma Any neoplasm (tumor) whether benign or malignant.

of the

lymphoid

tissue,

circulate in the bloodstream. (These

lymphocytes were

nally misidentified as monocytes: mononucleosis

=

origi-

a condi-

tion of monocytes.) Usually lasts 4 to 6 weeks.

Non-Hodgkin's lymphoma Includes all cancers of lymphoid tissues except Hodgkin's disease. Involves uncontrolled multiplication and metastasis of undifferentiated lymphocytes, with swelling of the lymph nodes, spleen, and Peyer's patches; other organs may eventually become involved.

The

fifth

most

common

cancer.

A high-grade

type,

young people, grows quickly but is responsive to chemotherapy; up to a 50% remission rate. A low-grade type, which affects the elderly, is resistant to chemotherapy and so is often fatal.

which primarily

affects

Sentinel node The first node that receives lymph drainage from a body area suspected of being cancerous. When examined for presence of cancer cells, this node gives the best indication of whether metastasis through the lymph vessels

has occurred.

Splenomegaly (sple"no-meg'ah-le mega = big) Enlargement due to accumulation of infectious microorganisms; typically caused by septicemia, mononucleosis, malaria, and ieukemia. ;

Mononucleosis A viral disease common in adolescents and young adults; symptoms include fatigue, fever, sore throat, and swollen lymph nodes. Caused by the Epstein-Barr virus, which is transmitted in saliva ("kissing disease") and specifically attacks B lymphocytes. This attack leads to a massive activation of T lymphocytes, which in turn attack the virusinfected B cells. Large numbers of oversized T lymphocytes

of the spleen

Tonsillitis (ton"si-li'tis ;

itis

= inflammation) Congestion

of

the tonsils, typically with infecting bacteria, which causes them to become red, swollen, and sore.

Chapter Summary Lymphatic

lymph nodes, and make up the lymphatic

other lymphoid orsystem. This system returns fluids that have leaked from the blood vascular system back to the blood, protects the body by removing foreign material from the lymph stream, and provides a site for 1.

vessels,

gans and tissues

immune

surveillance.

Lymphatic Vessels

(pp.

772-774)

Distribution and Structure of Lymphatic Vessels (pp. 1.

772-773)

— —

Lymphatic vessels form a one-way network lymphatic and ducts in which

capillaries, collecting vessels, trunks,

784

Maintenance of the Body

Unit IV

fluid flows only toward the heart. The right lymphatic duct drains lymph from the right arm and right side of the upper

body; the thoracic duct receives lymph from the rest of the body. These ducts empty into the blood vascular system at the junction of the internal jugular and subclavian veins in the neck.

773-774)

(pp.

The

flow of lymphatic fluid is slow; it is maintained by muscle contraction, pressure changes in the thorax, and (possibly) contractions of the lymphatic vessels. Backflow is prevented by valves.

Lymphatic capillaries are exceptionally permeable, admitand particulate matter from the interstitial

ting proteins space.

Pathogens and cancer

4.

cells

may

spread through the body

via the lymphatic stream.

Lymphoid Lymphoid

Cells

Cells

and Tissues (p.

(p.

775)

775)

1. The cells in lymphoid tissues include lymphocytes (immunocompetent cells called T cells or B cells), plasma cells

(antibody-producing offspring of B cells), macrophages (phagocytes that function in the immune response), and reticular cells that form the lymphoid tissue stroma.

Lymphoid Tissue Lymphoid

(p.

Lymphoid

3.

tissue

tissue

follicles. Follicles

B

is

reticular connective tissue.

be diffuse or packaged into dense

often display germinal centers (areas

(pp.

where

776-777)

Lymph

nodes, the principal lymphoid organs, are discrete encapsulated structures containing both diffusely arranged and dense reticular tissue. Clustered along lymphatic vessels, lymph nodes filter lymph and help activate the immune system. 1.

Structure of a 2.

Lymph Node

(pp.

The

enters the lymph nodes via afferent lymphatic exits via efferent vessels. There are fewer effer-

ent vessels; therefore, lymph flow stagnates within the lymph node, allowing time for its cleansing.

Other Lymphoid Organs

(pp.

777-779, 782)

Unlike lymph nodes, the spleen, thymus, tonsils, and filter lymph. However, most lymphoid organs contain both macrophages and lymphocytes. 1.

Peyer's patches do not

Spleen

(pp.

777-779)

2. The spleen provides a site for lymphocyte proliferation and immune function, and destroys aged or defective red blood cells and bloodborne pathogens. It also stores and releases the breakdown products of hemoglobin as necessary, stores platelets, and acts as a hematopoietic site in the fetus.

Thymus (p. 779) 3. The thymus is most

functional during youth. to

Its

hor-

become immunocompetent.

Lymphoid

Follicles

779-782)

(pp.

patches of the intestinal wall, lymphoid

4. Peyer's

of the appendix, tonsils of the pharynx,

follicles

follicles in

Developmental Aspects of the Lymphatic System (pp. 782-783) Lymphatics develop as outpocketings of developing veins. develops from endoderni; the other lymphoid organs derive from mesenchymal cells of mesoderm. 1.

The thymus

The thymus,

role in the

a fibrous capsule, a cortex, and a cortex contains mostly lymphocytes, which

and

the bronchial walls of the respiratory tract are known as MALT (mucosa-associated lymphatic tissue). They prevent pathogens in the respiratory and digestive tracts from penetrating the mucous membrane lining.

2.

776-777)

Each lymph node has

medulla.

777)

It

cells are proliferating).

Lymph Nodes

(p.

and

Tonsils and Aggregates of

775)

may

Lymph

Lymph Nodes

mones cause T lymphocytes

houses macrophages and a continuously changing population of lymphocytes. It is an important element of the immune system. 2.

Circulation in the vessels

skeletal

3.

cells.

3.

Lymph Transport 2.

immune responses; the medulla contains macrophages, which engulf and destroy viruses, bacteria, and other foreign debris, as well as lymphocytes and plasma

act in

3.

the first lymphoid organ to appear, plays a development of other lymphoid organs.

Lymphoid organs are populated by lymphocytes, which from hematopoietic tissue.

arise

Review Questions Multiple Choice/Matching

5.

Some questions have more than one correct answer. Select the best answer or answers from the choices given.)

Lymph nodes

are densely clustered in

ing body areas except

(a)

the brain,

(b)

all of the followthe axillae, (c) the

(

Lymphatic vessels (a) serve as sites for immune surveillance, (b) filter lymph, (c) transport leaked plasma proteins and fluids to the cardiovascular system, (d) are represented by vessels that resemble arteries, capillaries, and veins. 1.

2.

The

saclike initial portion of the thoracic duct

lacteal, (b) right

lymphatic duct,

(c)

cisterna chyli,

is

(d)

the

formed by overlapping endothelial cells, (b) the respiratory (c) the skeletal muscle pump, (d) greater fluid pres-

pump,

sure in the interstitial space.

The

structural

framework (b)

tissue, (d) adipose tissue.

The germinal centers in lymph nodes are largely sites of macrophages, (b) proliferating B lymphocytes, (c) T lym-

phocytes, 7.

The

(d) all

of these.

red pulp areas of the spleen are sites of (a) venous and red blood cells, (b) clustered lym-

(a)

lymph

3. Entry of lymph into the lymphatic capillaries is promoted by which of the following? (a) one-way minivalves

4.

6. (a)

sinuses, macrophages,

sac.

olar connective tissue,

groin, (d) the cervical region.

of lymphoid organs is (a) arehematopoietic tissue, (c) reticular

phocytes,

(c)

connective tissue septa.

8. The lymphoid organ that functions primarily during youth and then begins to atrophy is the (a) spleen, (b) thymus, (c) palatine tonsils, (d) bone marrow. 9. Collections of lymphoid tissue (MALT) that guard mucosal surfaces include all of the following except (a) appendix nodules, (b) the tonsils, (c) Peyer's patches, the thymus.

(d)

Chapter 20 Short Answer Essay Questions 10.

Compare and

contrast blood, interstitial fluid, and

lymph. 11.

Compare

the structure and functions of a

lymph node

to those of the spleen.

12. of

(a)

What anatomical

lymph through

a

characteristic ensures that the flow

lymph node

is

slow?

(b)

Why

is

this de-

sirable?

13. a

Why doesn't

The Lymphatic System

785

swollen and painful, and she is unable to raise it more than shoulder height, (a) Explain her signs and symptoms, (b) Can she expect to have relief from these symptoms in time?

How so? 2. A friend

tells you that she has tender, swollen "glands" along the left side of the front of her neck. You notice that she has a bandage on her left cheek that is not fully hiding large infected cut there. Exactly what are her swollen "glands," and how did they become swollen?

the absence of lymphatic arteries represent

problem?

MyA&P Thinking and Clinical Application Critical

Questions Mrs. Jackson, a 59-year-old woman, has undergone a left mastectomy (removal of the left breast and left axillary lymph nodes and vessels). Her left arm is severely 1.

radical

Explore with

MAP!1

Enhance your understanding

of the topics covered in this

chapter by accessing online media at

My A&P

(MAP) m

www.mariebmap.com. Navigate through exercises from InterActive Physiology® and PhysioEx"', quizzes, learning activities, case studies, and other study tools that will help you succeed in A&P.

a

The Immune System: nnate and Adaptive Body Defenses PART (pp.

1:

INNATE DEFENSES

787-796)

Humoral Immune Response 801-807)

(pp.

12. Define -

humoral immunity.

Surface Barriers: Skin and

Mucosae 1.

(pp.

Describe surface

and

barriers

13. Describe the process of clonal

787-788)

B

selection of a

membrane

14.

their protective

cell.

Recount the roles of plasma and memory cells in humoral immunity.

cells

functions.

and Chemicals (pp. 788-796) Internal Defenses: Cells

2.

cells in

killer

4.

antibody monomer, and

17.

Explain the function(s) of

inflammatory chemicals and

antibodies and describe clinical

indicate their specific roles.

uses of monoclonal antibodies.

Name

the body's antimicrobial

Cell-Mediated Immune

Response

function.

how

Explain

ADAPTIVE DEFENSES (pp. 796-824) PART

(pp.

807-818)

18. Define cell-mediated fever helps protect

the body.

how antigens affect immune system.

the

Define complete antigen, hapten, and antigenic

of

T

cells.

19. Describe

T

cell

functions in

the body.

20. Indicate the tests ordered before an organ transplant

prevent transplant rejection.

Homeostatic Imbalances of Immunity (pp. 818-822) 21. Give examples of

Follow antigen processing in the body.

Adaptive Immune System: An Overview (pp. 798-801)

Compare and origin,

contrast the

maturation process, and

general function of B and

T

immune

deficiency diseases and of hypersensitivity states.

Cells of the

9.

is

done, and methods used to

determinant 8.

immunity

and describe the process of activation and clonal selection

2:

Antigens (pp. 797-798) 6. Define antigen and describe

7.

name

the five classes of antibodies.

Describe the inflammatory

substances and describe their

5.

contrast active

16. Describe the structure of an

nonspecific body defense.

process. Identify several

Compare and

and passive humoral immunity.

Explain the importance of phagocytosis and natural

3.

15.

22. Cite factors involved in

autoimmune

disease.

Developmental Aspects of the Immune System (pp. 823-824) 23. Describe changes in

immunity

that occur with aging.

lymphocytes. 24. Briefly describe the role of the

10. Describe the role of

macrophages and phagocytes. 11. Define

and

immunocompetence

self-tolerance.

nervous system in regulating

other-

the

immune

response.

— Chapter 21

second of every day, an Every bacteria, fungi, and viruses

The Immune System: Innate and Adaptive Body Defenses

army of hostile swarms on our

PART

1:

787

INNATE DEFENSES

skin and yet we stay amazingly healthy most of the time. The body seems to have evolved a if you're not single-minded approach to such foes with us, you're against us! To implement that stance, it relics heavily on two intrinsic defense

Because they are part and parcel of our anatomy, you could say we come fully equipped with innate or nonspecific defenses. The mechanical barriers that cover body surfaces and the cells and chemi-

systems that act both independently and coopera-

in place at birth, ready to ward off invading pathogens (harmful or disease-causing microorganisms) and infection. Many times, our innate defenses alone are able to destroy pathogens and ward

—

tively to provide resistance to disease, or

[immun = free). 1. The innate (nonspecific) system,

immunity

lowly foot soldier, is always prepared, responding within minutes to protect the body from all foreign substances. This system has two "barricades." The first line of defense is the external body membranes intact skin and mucosae. The second line of defense called into action whenever the first line has been penetrated, uses antimicrobial proteins, phagocytes, and other cells to inhibit the invaders' spread throughout the body. The hallmark of the second line of defense is inflammation. like a

2. The adaptive (or specific) defense system* is more like an elite fighting force equipped with

high-tech weapons that attacks particular foreign substances and provides the body's third line of defense. This defensive response takes considerably more time to mount than the innate response. Al-

though we consider them separately, the adaptive and innate systems always work hand in hand. Although certain organs of the body (notably lymphoid organs) are intimately involved in the immune response, the immune system is a functional system rather than an organ system in an anatomical sense. Its "structures" are a diverse array of molecules plus trillions of immune cells (especially lymphocytes), that inhabit lymphoid tissues and circulate in body fluids. When the immune system is operating effectively it protects the body from most infectious mfcroorganisms, cancer cells, and transplanted organs or grafts. It does this both directly, by cell attack, and indirectly, by releasing mobilizing chemicals and protective antibody molecules.

on the

cals that act

initial internal battlefronts are

off infection. In others, the

tem

adaptive

called into action to reinforce

is

immune

sys-

and enhance

the nonspecific mechanisms. In either case, the innate defenses reduce the workload of the adaptive system by preventing entry and spread of microorganisms in the body.

Surface Barriers:

Mucosae

Skin and

—

The body's first line of defense the skin and the mucous membranes, along with the secretions these membranes produce is highly effective. As long as

—

unbroken, this heavily keratinized presents a formidable physical barrier to most microorganisms that swarm on the the epidermis

epithelial

is

membrane

skin. Keratin

is

and bases and

most weak acids enzymes and toxins. In-

also resistant to

to bacterial

mucosae provide similar mechanical barriers within the body. Recall that mucous membranes tact

body

line all

cavities that

open

to the exterior, the

respiratory, urinary, and reproductive Besides serving as physical barriers, these ep-

digestive, tracts. ithelial

membranes produce

a variety of protective

chemicals: 1

.

The

(pH 3 to 5) inhibits growth and sebum contains chemicals that

acidity of skin secretions

bacterial

are toxic to bacteria. Vaginal secretions of adult fe-

males are also very 2.

acidic.

The stomach mucosa

secretes a concentrated hy-

drochloric acid solution and protein-digesting en-

zymes. Both

kill

microorganisms.

Saliva, which cleanses the oral cavity and teeth, and lacrimal fluid of the eye contain lysozyme, an 3.

enzyme 4.

that destroys bacteria.

Sticky

mucus

traps

many microorganisms

that

enter the digestive and respiratory passageways. * Sometimes the term immune system is equated with the adaptive system only. However, recent research has shown that (1) many defensive molecules are released and recognized hy both the innate and adaptive arms (2) the innate responses are not as nonspecific as once thought and may have specific pathways to target certain foreign substances; and (3) proteins released during innate responses alert cells of the adaptive system to the presence of specific foreign molecules in the body. ;

The tural

respiratory tract

mucosae

also have struc-

modifications that counteract potential

in-

vaders. Tiny mucus-coated hairs inside the nose trap

inhaled particles, and cilia on the mucosa of the upper respiratory tract sweep dust- and bacteria-laden mucus toward the mouth, preventing it from entering the lower respiratory passages,

where the warm,

788

Unit IV

Maintenance of the Body

moist environment provides an ideal rial

site for bacte-

growth.

of Phagocytosis

A

Although the surface barriers are quite effective, they are breached occasionally by small nicks and cuts resulting, for example, from brushing your teeth or shaving. When this happens and microorganisms invade deeper tissues, the internal innate defenses

come

Mechanism

into play.

phagocyte engulfs particulate matter much the way an amoeba ingests a food particle. Flowing cytoplasmic extensions bind to the particle and then pull it inside, enclosed within a membrane-lined vacuole. The phagosome thus formed is then fused with a lysosome to form a phagolysosome (steps ©-(D in Figure 21.1b).

Phagocytic attempts are not always successful. In order for a phagocyte to accomplish ingestion,

Internal Defenses: Cells

and Chemicals

The body uses an enormous number

of nonspecific

and chemical devices to protect itself, including phagocytes, natural killer cells, antimicrobial proteins, and fever. The inflammatory response cellular

macrophages, mast cells, all types of white blood cells, and dozens of chemicals that kill pathogens and help repair tissue. All these protective ploys identify potentially harmful substances by recognizing surface carbohydrates unique to infectious organisms (bacteria, viruses, and fungi). Fever is also an innate protective response. enlists

Phagocytes Pathogens that get through the skin and mucosae into the underlying connective tissue are confronted by phagocytes [phago = eat). The chief phagocytes are

macrophages

("big eaters"),

which

derive

from

white blood cells called monocytes that leave the bloodstream, enter the tissues, and develop into macrophages. Free macrophages, like the alveolar macrophages of the lungs and dendritic cells of the epidermis, wander throughout the tissue spaces in search of cellular debris or "foreign invaders." Fixed macrophages like Kupffer cells in the liver and microglia of the brain are permanent residents of particular organs. Whatever their mobility, all macrophages are similar

structurally

and

functionally.

Neutrophils, the most abundant type of white blood cell, become phagocytic on encountering infectious material in the tissues. Eosinophils, another type of white blood cell, are only weakly phagocytic, but they are important in defending the body against parasitic worms. When they encounter such parasites, eosinophils position themselves against the worm and discharge the destructive contents of their large cytoplasmic granules all over their prey. Recently

more associated with their role in have been shown to have a striking ability

mast

allergies,

cells,

to bind with, ingest,

Although mast

wide range of bacteria. are not normally included in

and

cells

kill a

listings of professional phagocytes,

capabilities.

they share their

adherence must occur. The phagocyte must first adhere or cling to the pathogen, a feat made possible by recognizing the pathogen's carbohydrate "signature." Recognition is particularly difficult with microorganisms such as pneumococcus, which have an external capsule made of complex sugars. These pathogens can sometimes elude capture because phagocytes cannot bind to their capsules. Adherence is both more probable and more efficient when complement proteins and antibodies coat foreign particles, a process called opsonization ("to make tasty"), be-

cause the coating provides "handles" to which phagocyte receptors can bind. Sometimes the way neutrophils and macrophages kill ingested prey is more than simple digestion by lysosomal enzymes. For example, pathogens such as the tuberculosis bacillus and certain parasites are resistant to lysosomal enzymes and can even multiply

within the phagolysosome. However, when the macrophage is stimulated by chemicals released by

immune

cells,

additional

enzymes

are activated

that produce the respiratory burst, an event that liberates a deluge of free radicals (including nitric oxide), that

have potent

cell-killing ability.

More

widespread cell killing is caused by oxidizing chemicals (H 2 0 2 and a substance identical to household bleach) released into the extracellular + space. These, in turn, promote K entry into the phagolysosome, causing its pH to rise and creating hyperosmolar conditions which activate proteindigesting enzymes that digest the invader. Neutrophils also produce antibiotic-like chemicals, called defensins (see p. 655), that pierce the pathogen's membrane. Unhappily, the neutrophils also destroy themselves in the process,

macrophages, which rely only on killing, can go on to kill another day.

whereas

intracellular

Natural Killer Cells Natural killer (NK) cells, which "police" the body in blood and lymph, are a unique group of defensive cells that can lyse and kill cancer cells and virusinfected body cells before the adaptive immune system activated. Sometimes called the "pit bulls" of the cells are part of a small group of defense system, large granular lymphocytes. Unlike lymphocytes of is

NK

The Immune System: Innate and Adaptive Body Defenses

Chapter 21

789

(T) Microbe adheres to phagocyte

Phagocyte forms pseudopods

(2)

that

eventually engulf the particle

Phagocytic vesicle containing antigen

(phagosome)

Phagocytic vesicle is fused with a lysosome

Phagolysosome (4) Microbe

in

fused vesicle

and digested by

is killed

lysosomal enzymes within the phagolysosome, leaving a residual body Residual body

(D

Indigestible

and

residual material is

5>*A

removed by

exocytosis

(b)

(a)

FIGURE

21

Phagocytosis,

.1

(a) In this

scanning electron micrograph (2600X), a

macrophage uses

its

bacteria toward

(b) Events of phagocytosis.

the adaptive

it.

long cytoplasmic extensions to pull sausage-shaped

immune

system, which recognize and

react only against specific virus-infected or cells,

NK cells

are far less picky.

tumor

They can eliminate

1

.

detecting the lack of "self" cell

by recognizing certain surface sugars on the

Prevents the spread of damaging agents to nearby

tissues

and pathogens

2.

Disposes of

3.

Sets the stage for repair

a variety of infected or cancerous cells, apparently

by surface receptors and

E. coli

The

target

cell debris

four cardinal signs of short-term, or acute,

brane and release of cytolytic chemicals called

inflammation are redness, heat [inflam = set on fire), and pain (Figure 21.2). If the inflamed area is a joint, joint movement may be hampered temporarily. This forces the injured part to rest, which aids healing. Some authorities consider impairment

perforins. Shortly after perforin release, channels ap-

of function to be the fifth cardinal sign of acute in-

The name

cell.

specificity of

NK

cells

"natural" killer cells reflects this non-

NK cells. are not phagocytic. Their

killing involves

an attack on the

pear in the target disintegrates.

that

swelling,

membrane and

nucleus also secrete potent chemicals

cell's

NK cells

mode of mem-

target cell's

its

Vasodilation and Increased Vascular Permeability

enhance the inflammatory response.

The inflammatory

Inflammation: Tissue Response to Injury

process begins with a chemical

"alarm" as a flood of inflammatory chemicals are

Macrophages boundary tissues such as epithelining the gastrointestinal and respira-

released into the extracellular fluid.

The inflammatory response body tissues are

flammation.

whenever injured by physical trauma fa blow), is

triggered

intense heat, irritating chemicals, or infection by viruses, fungi, or bacteria.

The inflammatory

sponse has several beneficial

effects:

re-

(and cells of certain lial

cells

tory tracts) bear surface

membrane

receptors, called

Toll-like receptors (TLRs), that play a central role in

triggering

immune

responses. So far ten types of

790

Unit IV

Why

Maintenance of the Body

become

important that the capillaries

is it

leaky

during the inflammatory response?

*

Tissue injury

Release

chemical mediators

of

(histamine, complement, kinins, prostaglandins, etc.)

o

o

o

o o

•

o

o

Release of leukocytosisinducing factor • • • • • • a •

•

o

'

o

„

o

to

o

•

•

•

Leukocytosis (increased numbers of white blood cells in bloodstream)

o

0

Increased capillary

Attract neutrophils,

permeability

monocytes and lymphocytes to area (chemotaxis) Migration to

Local hyperemia

Capillaries leak fluid

(increased blood flow to area)

(exudate formation)

injured area

»

Blood flow slows

Margination (leukocytes cling to capillary walls)

Heat

Redness

I

!

Diapedesis (leukocytes pass through capillary walls) Increased oxygen

Leaked

and

fluid in

nutrients

Leaked

protein-rich

tissue

spaces

clotting

proteins

Phagocytosis Walling-off process

Pain

I

Swelling

(blood clots wall off

area to prevent injury to surrounding area)

Increased temperature increases metabolic

limitation of

Temporary

movement

fibrin

patch forms scaffolding for repair

T

Flowchart of events

acute inflammation are shown in

some

cases constitutes a

paiueyu/

aiji

(by neutrophils, short-term;

by macrophages, long-term) 1

Possible temporary joint

21 .2

pathogens cells

Pus may form

rate of cells

FIGURE

of

and dead tissue

in

fifth

in

inflammation. The four cardinal signs of is limitation of joint movement, which

red boxes, as

cardinal sign (impairment of function).

jajua oi saipoquue pue 'suidiojd 6u\iiop-poo\q

's\udijinu 'uaS/fxo Buiuieiuoo ajejj/y sjoiu s/wo//e s/uj_

Area cleared of debris

— Thp IMC Immiinp U 1

Phantpr ?1 v~ luU LCI *—

1

1

TABLE

21.1

/

1

1

1

1

1

1

1

1

1

^\/Qtpnrv J y old 1

1

.

ll ll

L/clfcMlbfcrb

/

Chemical

Source

Physiological Effects

Histamine

Granules of basophils and mast cells; released in response to mechanical injury, presence of certain microorganisms, and chemicals released by neutrophils

Promotes vasodilation of local arterioles; increases permeability of local capillaries,

Kinins

A plasma

(bradykinin an d others)

enzyme kallikrein found in plasma, urine, saliva, and in lysosomes of neutrophils and other types

protein, kininogen,

is

Same

cleaved by the

Secreted by platelets and endothelial

Platelet-derived

See Table 21.2

(p.

Cytokines

See Table 21.4

(pp.

human TLRs have been

and prompt neutrophils to release lysosomal enzymes, thereby enhancing generation of more kinins; induce pain blood vessels to effects of other inflammatory mediators; one of the intermediate steps of prostaglandin generation produces free radicals, which themselves can cause inflammation; induce pain Sensitize

Stimulates fibroblast activity and repair of

cells

813-814)

identified,

tem. Injured and stressed tissue cells, phagocytes, lymphocytes, mast cells, and blood proteins are all sources of inflammatory mediators, the are

most impor-

histamine (his'tah-men), kinins

prostaglandins (PGs) (pros"tah-glan'dinz),

and complement, as well as cytokines. Though some of these mediators have individual inflammatory roles as well (see Table 21.1), they

all

cause

small blood vessels in the injured area to dilate. As into the area, local hyperemia (congestion with blood) occurs, accounting for the redness and heat of an inflamed region. The liberated chemicals also increase the perme-

more blood flows

Consequently, exudate fluid containing clotting factors and antibodies seeps from the blood into the tissue spaces. This exudate causes the local edema (swelling) that presses on adjacent nerve endings, contributing to a sensation of pain. Pain also results from the release of bacterial toxins, lack of nutrition to cells in the ability of local capillaries.

area, and the sensitizing effects of released prostaglandins and kinins. Aspirin and some other

anti-inflammatory drugs produce their analgesic (pain-reducing) effects by inhibiting prostaglandin synthesis.

tissues

793)

each recognizing a specific class of attacking microbe. For example, one type responds to a glycolipid in cell walls of the tuberculosis bacterium and another to a component of gram-negative bacteria such as salmonella. Once activated, a TLR triggers the release of chemicals called cytokines that promote inflammation and attract WBCs to the scene. But macrophages are not the only sort of recognition "tool" in the innate sys-

(ki'ninz),

as for histamine; also induce chemotaxis

damaged

Complement

which

I

of leukocytes

growth factor

tant of

/

promoting exudate formation

Fatty acid molecules produced from arachidonic acid; found in all cell membranes; generated by lysosomal enzymes of neutrophils and other cell types

Prostaglandins " (PGs)

'

DUUy

Inflammatory Chemicals

of cells; cleavage releases active kinin peptides

i

Idle dliu AAUdLHIVtr

Although edema

may seem

detrimental,

it isn't.

The

surge of protein-rich fluids into the tissue spaces (1) helps to dilute harmful substances that may be present, (2) brings in the large quantities of oxygen and nutrients needed for repair, and (3) allows the entry of clotting proteins (Figure 21.2). The

form a gel-like fibrin mesh that forms a scaffolding for permanent repair. This isolates the injured area and prevents the spread of bacteria and other harmful agents into clotting proteins in the tissue space

surrounding tissues. At inflammatory sites where an epithelial barrier has been breached, an additional chemical enters the battle B-defensins. These broad-spectrum antibiotic-like chemicals are continuously present in epithelial mucosal cells in small amounts and help maintain the sterile environment of the body's internal passageways (urinary tract, respiratory bronchi, etc.). However, when the mucosal surface is abraded or penetrated and the underlying connective tissue becomes inflamed, B-defensin output in-

—

creases dramatically, helping to control bacterial and fungal colonization in the exposed area.

Phagocyte Mobilization Soon after inflammation begins, the damaged area is invaded by more phagocytes neutrophils lead, followed by macrophages. If the inflammation was provoked by pathogens, a group of plasma proteins

—

known

complement (discussed shortly) is activated and elements of adaptive immunity (lymphocytes and antibodies) also invade the injured site. The process by which phagocytes are mobilized to as

infiltrate the injured site is illustrated in Figure 21.3.

792

Unit IV

Maintenance of the Body

F+GURE

21 .3

Phagocyte mobilization. When

leukocytosis-inducing factors are released by injured cells at

an inflamed

site,

CD neutrophils

are released

from the bone marrow to the blood. Because blood at the inflammatory site loses fluid, blood flow slows locally and the neutrophils roll along the vascular endothelium. Margination begins as neutrophil cell adhesion

©

molecules (CAMs) cling to those of the capillary cells, and then diapedesis occurs as the neutrophils squeeze through the capillary walls. Positive chemotaxis is the continued migration toward

@

endothelial

the

site

where inflammatory chemicals are released by

neutrophils.

help

(D Leukocytosis. Chemicals

called leukocytosis-

inducing factors released by injured cells promote rapid release of neutrophils from red bone marrow, and within a few hours the number of neutrophils in blood increases four to five fold. This increase in

WBCs,

called leukocytosis, is a characteristic of in-

flammation. of the

tremendous out-

pouring of fluid from the blood into the injured area, blood flow in the region slows and the neutrophils begin to roll along the capillary endothelium as if "tasting" the local environment. In inflamed areas, the endothelial cells sprout cell adhesion molecules (CAMs) called selectins. These provide footholds (signal that "this is the place") for

CAMs (integrins) When the com-

surfaces of the neutrophils.

plementary

Once

at the inflamed site, the neutrophils

the area of pathogens and cellular debris.

attract the neutrophils

and other white blood cells to Within an hour after the in-

the site of the injury. flammatory response has begun, neutrophils have collected at the site

and are devouring any foreign

material present.

As the counterattack continues, monocytes folarea. Monocytes are

low neutrophils into the injured

(D Margination. Because

on the

rid

®

CAMs

bind together, the neutrophils

cling to the inner walls of the capillaries

capillary venules. This

phenomenon

is

and post-

known

as

margination or pavementing. Diapedesis. The continued chemical signaling prompts the neutrophils to squeeze through the capillary walls, a process called diapedesis or emigration.

fairly

poor phagocytes, but within

1

2 hours of leav-

ing the blood and entering the tissues, they swell and

develop large numbers of lysosomes, becoming macrophages with insatiable appetites. These latearriving macrophages replace the neutrophils on the

Macrophages are the central actors in the final disposal of cell debris as an acute inflammation subsides, and they predominate at sites of prolonged, or chronic, inflammation. The ultimate goal of an inflammatory response is to clear the injured area of pathogens, dead tissue cells, and any other debris so that tissue can be repaired. Once this is accom-

battlefield.

plished, healing usually occurs quickly.

(|)

@

Chemotaxis. Neutrophils usually migrate randomly, but inflammatory chemicals act as homing devices, or more precisely chemotactic agents, that

HOMEOSTATIC IMBALANCE In severely infected areas, the battle takes a considerable toll on both sides, and creamy, yellow pus, a

mixture of dead or dying neutrophils, broken-down

The Immune System: Innate and Adaptive Body Defenses

Chapter 21

TABLE 21.2

^

Summary

of Nonspecific

793

Body Defenses

Category/Associated Elements

Protective

First Line

of Defense: Surface

Intact skin

epidermis

Acid mantle

Membrane

Barriers

Forms mechanical body

barrier that prevents entry of

Skin secretions (perspiration

growth;

sebum

mucous membranes

pathogens and other harmful substances

and sebum) make epidermal surface

acidic,

which

into

inhibits bacterial

also contains bactericidal chemicals

Provides resistance against acids,

Keratin Intact

Mechanism

Form mechanical

alkalis,

and

bacterial

barrier that prevents entry of

enzymes

pathogens

and digestive

Mucus

Traps microorganisms

Nasal hairs

Filter

Cilia

Propel debris-laden

Gastric juice

Contains concentrated hydrochloric acid and protein-digesting enzymes that destroy pathogens in

in

respiratory

and trap microorganisms

in

nasal passages

mucus away from lower

growth of most bacteria and fungi

Inhibits

Lacrimal secretion

Continuously lubricate and cleanse eyes enzyme that destroys microorganisms

Normally acid

Urine

respiratory passages

stomach

Acid mantle of vagina

(tears); saliva

tracts

pH

inhibits bacterial

in

female reproductive

(tears)

and

tract

oral cavity (saliva); contain lysozyme,

growth; cleanses the lower urinary tract as

an

flushes from the

it

body

Second Line of Defense: Nonspecific

and Chemical Defenses

Engulf and destroy pathogens that breach surface contribute to immune response

Phagocytes

Natural

Cellular

killer cells

Promote

cell lysis

depend on Inflammatory response

by direct

cell

membrane

barriers;

macrophages

attack against virus-infected or cancerous

specific antigen recognition;

do not

exhibit a

body

cells;

also

do not

memory response

Prevents spread of injurious agents to adjacent tissues, disposes of pathogens and dead and promotes tissue repair; chemical mediators released attract phagocytes (and immunocompetent cells) to the area

tissue cells,

Antimicrobial proteins Interferons

(a,

(3, -y)

Proteins released by virus-infected cells that protect uninfected tissue cells from

mobilize

Complement

viral

takeover;

immune system

Lyses microorganisms, enhances phagocytosis by opsonization, and intensifies inflammatory and

immune responses Fever

Systemic response initiated by pyrogens; high body temperature inhibits microbial multiplication repair processes

and enhances body

and living and dead pathogens, may accumulate in the wound. If the inflammatory mechanism fails to clear the area of debris, the sac of pus may be walled off by collagen fibers, forming an tissue cells,

abscess. Surgical drainage of abscesses

is

often nec-

may

harbor pathogens walled

off in

granulomas

for

years without displaying any symptoms. However, if the person's resistance to infection is ever compro-

mised, the bacteria may be activated and break out, leading to clinical disease symptoms. •

essary before healing can occur.

such as tuberculosis bacilli, that are by macrophages escape the effects of prescription antibiotics by remaining snugly enclosed within their macrophage hosts. In such cases, infectious granulomas form. These tumorlike growths contain a central region of infected macrophages surrounded by uninfected macrophages and an outer fibrous capsule. A person Bacteria,

resistant to digestion

Antimicrobial Proteins

A variety of antimicrobial

proteins enhance the inattacking microorganisms directly defenses by nate or by hindering their ability to reproduce. The most important of these are interferon and complement

proteins (Table 21.2).

794

Unit IV

Maintenance of the Body

.The IFNs are a family of related proteins, produced by a variety of body cells, each having a slightly different physiological effect. Lymphocytes secrete

Virus

gamma

(7) or immune, interferon, but most other leukocytes secrete alpha (a) interferon. Fibroblasts secrete beta ((3) interferon which is particularly active in reducing inflammation. Besides their antiviral ef-

fects, interferons activate

NK

macrophages and mobilize

Because both macrophages and NK cells can act directly against malignant cells, the interferons play some anticancer role. The IFNs have found a niche as antiviral agents. Alpha IFN is used to treat genital warts (caused by the herpes virus) and it is the first drug to have some success in combating hepatitis C (spread via blood and sexual intercourse), the most common and most dreaded form of hepatitis. The IFNs are also used against devastating viral infections in organ transcells.

plant patients.

Complement Interferon binding

stimulates cell to Interferon turn

molecules produced

Host Cell

is killed

for

Host Cell 2

1

Infected by virus;

makes

on genes

antiviral proteins

interferon;

or simply complement, refers to a group of at least 20 plasma proteins that normally circulate in the blood in an inactive state. These proteins include CI through C9, factors B, D, and P, plus several regulatory proteins. Complement provides a major mechanism for destroying

foreign substances in the body. Its activation un-

Entered by interferon from cell 1 interferon induces changes that

leashes chemical mediators that amplify virtually all aspects of the inflammatory process. Another effect

protect

of

;

by virus

The term complement system,

it

complement

activation

is

that bacteria and cer-

by cell lysis. (Luckily equipped with proteins that inactivate complement.) Although complement is a nontain other cell types are killed

own

our

FIGURE 21.4

The interferon mechanism against

viruses.

cells are

specific defensive

mechanism,

(enhances) the effectiveness

"complements" oiboth innate and adapit

tive defenses.

Complement can be Interferon

—

ways outlined

Viruses essentially nucleic acids surrounded by a protein coat lack the cellular machinery to generate ATP or synthesize proteins. They do their "dirty work" or damage in the body by invading tissue cells

—

and taking over the

cellular metabolic machinery needed to reproduce themselves. Although the infected cells can do little to save themselves, some can secrete small proteins called interferons (IFNs; in"ter-fer'onz) to help protect cells that have not yet been infected. The IFNs diffuse to nearby cells,

where they stimulate synthesis of a protein known as PKR, which then "interferes" with viral replication in the still-healthy cells by blocking protein synthesis at the ribosomes (Figure 21.4). Because

protection

is

not virus-specific,

IFN

IFNs produced

against a particular virus protect against a variety of other viruses.

activated by the

in Figure 21.5.

The

two pathpathway

classical

involves antibodies, water-sofuble protein molecules

immune system

produces to fight off foreign invaders. The classical pathway depends on the binding of antibodies to the invading organisms and the subsequent binding of CI to the microorganism-antibody complexes, a step called complement fixation (described on pp. 805-806). that the adaptive

The

alternative

pathway

is

triggered

when factors B,

D, and P interact with polysaccharide molecules present on the surface of certain microorganisms. Each pathway involves a cascade in which complement proteins are activated in an orderly se-

—

quence each step causing catalysis of the next step. The two pathways converge on C3, cleaving it into C3a and C3b. This event initiates a common terminal pathway that causes cell lysis, promotes phagocytosis, and enhances inflammation.

The Immune System: Innate and Adaptive Body Defenses

Chapter 21 Which pathway can occur without the need immune response?

?

for

795

an

adaptive

Complement

FIGURE 21.5

Classical pathway antigen-antibody

activation. The classical pathway,

mediated by designated C1 1

1

complement

-C9

Alternative pathway Microorganisms' cell wall polysaccharides.

complex

proteins

+

(C1 incorporates

three proteins) requires antigen-antibody interactions.

occurs

The

alternative

when plasma

C4

pathway

C2

Factor B, Factor D,

and Factor P (properdin)

proteins called

and P interact with polysaccharides on the cell walls of certain bacteria and fungi. The two pathways converge to activate C3 (cleaving it into C3a and C3b), a step that

Complex

factors B, D,

initiates a

common

terminal sequence.

Once bound to the target cell's surface, C3b initiates the remaining steps of complement activation. These steps result in the incorporation of MAC, the membrane attack complex (components C5b, and C6 to C9), into the target cell's membrane, creating

a

lesion that causes cell

also

C3b

C3b C5a Opsonization: coats bacterial surfaces,

funnel-shaped

stimulates histamine release, increased




/

results

Positive

MHC

(react

of survivors

restriction

weakly with

Thymic

FIGURE those T

21 .7

T

cell

cells that are

selection

Tcell

cell

in

the thymus,

able to recognize self

MHC

are allowed to continue the maturation process.

(a)

During positive selection, only

(with or

without bound peptide)

Those that

fail

this test

apoptosis. (b) Negative selection identifies T cells that are self-tolerant. react too vigorously with self

MHC

MHC)

are selected against

undergo Those that

and eliminated.

cells will proliferate

Antigen-Presenting Cells

Only some of programmed to

The major

and mount the attack against it. the antigens our lymphocytes are

invade our bodies. Consequently only some members of our army of immunocompetent cells are mobilized in our lifetime. The others are forever idle. After becoming immunocompetent, the naive (still immature) T cells and B cells are exported to the lymph nodes, spleen, and other secondary lymphoid organs, where the encounters with antigens occur (Figure 21.8). Then, when the lymphocytes bind with recognized antigens, the lymphocytes complete their differentiation into fully functional mature, antigen-activated

resist will ever

—T

—

cells

'Mdj e aiueu oj sjjdo

and B

g pue

cells.

's//ao

onupuep

'saBeLfdojoe^j

role of

antigen-presenting cells in im-

munity is to engulf antigens and then present fragments of these antigens, like signal flags, on their own surfaces where they can be recognized by T cells

— that

is,

they present antigens to the

will destroy the antigens.

The major

cells that

types of cells

APCs

are dendritic cells present in connecLangerhans' cells of the skin epidermis, macrophages, and activated B lymphocytes. Notice that all these cell types are in sites that make it very easy to encounter and process antigens. Dendritic cells are at the body's frontiers, best situated to act as mobile sentinels. Macrophages are widely distributed throughout the lymphoid organs and connective tissues. Besides their antigen-

acting as

tive tissues,

presenting

role, dendritic cells

and macrophages also

800

Unit IV

What

is

Maintenance of the Body

the advantage of having lymphocytes that are

mobile rather than fixed

in

the lymphoid organs?

Site of

lymphocyte

Site of

development

origin

of

immunocompetence as B

or

T

cells;

primary lymphoid organs Site of antigen challenge

and final B and T

differentiation to activated

(T)

cells

Lymphocytes destined to become T cells migrate thymus and develop immunocompetence

to the

there.

B

cells

develop immunocompetence

in

red

bone marrow.

thymus or bone marrow as naive immunocompetent cells, lymphocytes "seed" the lymph nodes, spleen, and other lymphoid tissues where the antigen challenge occurs.

Immunocompetent, but

still

(2) After leaving the

naive,

lymphocyte migrates via

blood

(D

lymphocytes circulate continuously in the bloodstream and lymph and throughout the lymphoid organs of the body.

Activated

immunocompetent B and T cells recirculate

Mature (antigen-activated) immunocompetent

in

blood and lymph

FIGURE 21.8

Lymphocyte

marrow. (Note that red marrow of long

bones

in

Immature lymphocytes arise in red bone not found in the medullary cavity of the diaphysis

traffic. is

adults.)

secrete soluble proteins that activate

T

cells. Acti-

vated T cells, in turn, release chemicals that rev up the mobilization and maturation of dendritic cells and prod macrophages to become activated macrophages, true "killers" that are insatiable phagocytes and secrete bactericidal chemicals. As you will see, interactions between various lymphocytes, and between lymphocytes and APCs, underlie virtually all phases of the immune response.

B o/njpads japeojq

e l/j/m

s//a3

pejuoo

Apoq J9uio pue suoBiiue ojui aiuoo o] aisuj s/v\o//e

p }/

Although APCs and lymphocytes are found throughout each lymphoid organ, specific cells tend to be

more numerous

in certain areas. For example,

lymph nodes house mostly and T dendritic cells and B cells tend to populate the germinal centers (see Figure 20.4, p. 776), whereas relatively more macrophages are clustered around the medullary sinuses. Macrophages tend to remain fixed in the lymphoid organs, as if waiting for antigens to come to them. But lymphocytes, esthe paracortical areas of cells,

T

(which account for 65-85% of bloodborne lymphocytes), circulate continuously pecially the

cells

Chapter 21

The Immune System: Innate and Adaptive Body Defenses

This circulation greatly increases a lymphocyte's chance of coming into contact with antigens located in different parts of the body, as well as with huge numbers of macrophages and other lymphocytes. Although lymphocyte recirculation appears to be random, the lymphocyte emigration to the tissues where their protective services are needed is highly specific, regulated by throughout

homing

the

signals

endothelial

body.

(CAMs)

displayed

on vascular

Because lymph capillaries pick up proteins and pathogens from nearly all body tissues, immune cells in lymph nodes are in a strategic position to encounter a large variety of antigens. Lymphocytes and APCs in the tonsils act primarily against microorganisms that invade the oral and nasal cavities, whereas the spleen acts as a filter to trap bloodborne antigens. In addition to

T cell recirculation and passive de-

livery of antigens to

a third delivery

lymphoid organs by lymphatics,

— migration of dendritic lymphoid organs — may be an

mechanism

to secondary even more important way of ensuring that the immune cells encounter invading antigens. With their cells

long veil-like extensions, dendritic cells are very efficient antigen catchers, and once they have internalized antigens by phagocytosis, they enter nearby

lymphatics to get to the lymphoid organ where they will present the antigens to T and B cells. Indeed, recent research suggests that the dendritic cells are the true initiators of adaptive immunity.

summary, the two-fisted adaptive immune system uses lymphocytes, APCs, and specific molecules to identify and destroy all substances both living and nonliving that are in the body but not In

—

—

recognized as

self.

threats depends

cross-link adjacent receptors together. Antigen binding is quickly followed by receptor-mediated endocytosis of the cross-linked antigen-receptor

These events

(plus

some

The

on the

system's response to such

ability of its cells

nize antigens in the body by binding to

(

1

)

to recog-

them and

(2)

communicate with one another so that the whole system mounts a response specific to those antigens.

to

Humoral Immune Response The antigen challenge, the first encounter between an immunocompetent but naive lymphocyte and an invading antigen, usually takes place in the spleen or in a lymph node, but it may happen in any lymphoid

lymphocyte is a B cell, the challenging antigen provokes the humoral immune response, in which antibodies are produced against the challenger. tissue. If the

Clonal Selection and Differentiation of B Cells

An immunocompetent

but naive B lymphocyte is activated (stimulated to complete its differentiation) when antigens bind to its surface receptors and

complexes.

interactions with

T

cells

described shortly) trigger clonal selection (klo'nul).

That

is,

the events stimulate the B

cell to

grow and

then multiply rapidly to form an army of cells all exactly like itself and bearing the same antigenspecific receptors (Figure 21.9).

cestor

The

resulting family

descended from the same an-

of identical cells, all

cells.

801

called a clone.

the antigen that does the selecting in clonal selection by "choosing" a cell,

is

It

is

lymphocyte with complementary receptors. Most cells of the clone become plasma cells, the antibody- secreting effector cells of the humoral response. Although B cells secrete limited amounts of antibodies, plasma cells develop the elaborate internal

machinery

(largely

rough endoplasmic

re-

ticulum) needed to secrete antibodies at the unbe-

2000 molecules per second. Each plasma cell functions at this breakneck pace for 4 to 5 days and then dies. The secreted antibodies, each with the same antigen-binding properties as the receptor molecules on the surface of the parent B cell, circulate in the blood or lymph, where they bind to free antigens and mark them for destruction by other specific or nonspecific mechanisms. Clone cells that do not differentiate into plasma cells become long-lived memory cells that can mount an almost immediate humoral response if they encounter the same antigen again at some future time (see Figure 21.9). lievable rate of about

Immunological The

Memory and differentiation just deprimary immune response,

cellular proliferation

scribed constitute the

which occurs on

exposure to a particular antigen. typically has a lag period of 3 to 6 days after the antigen challenge. This lag period mirrors the time required for the few B cells specific for that antigen to proliferate and for their offspring to differentiate into plasma cells. After the mobilization period, plasma antibody levels rise, reach peak levels in about 10 days, and then decline (Figure 21.10). If (and when) someone is reexposed to the same antigen, whether it's the second or the twentysecond time, a secondary immune response occurs. Secondary immune responses are faster, more prolonged, and more effective, because the immune system has already been primed to the antigen, and sensitized memory cells are already in place "on alert." These memory cells provide what is comfirst

The primary response

called immunological memory. Within hours after recognition of the "old enemy" antigen, a new army of plasma cells is being generated. Within 2 to 3 days the antibody

monly

802

Unit IV

Maintenance of the Body

Antigen

Primary Response (initial

encounter

Antigen binding

with antigen

a receptor on a B lymphocyte

to

specific

B lymphocytes with non-complementary receptors remain inactive)

B lymphoblasts

Plasma

Memory

cells

Secreted antibody

molecules

B

V V \* t

t

Secondary Response (can be years

Clone

later)

cell

t

rj. Subsequent challenge

of cells

by

identical to

same

antigen

ancestral cells

Plasma cells

Secreted

JL

antibody

FIGURE 21.9 B

^

*^

molecules

JL

«^

Clonal selection of a

The initial meeting between a B and antigen stimulates the primary

cell.

cell

response

in

which the B

cell proliferates

forming many identical B cells clone), most of which differentiate

rapidly, (a

into

antibody-producing plasma

Memory B cells

A.

cells.

ations.) Cells that

much

primary response. Secondary response antibodies not only bind with greater affinity (more tightly), but their blood levels remain high for weeks to months. (Hence, when the appropriate chemical signals are present, plasma cells can keep functioning for much longer than the 4 to 5 days seen in primary responses.)

Memory

cells persist for

long periods in

retain their capacity to produce

powerful secondary humoral responses for life. The same general phenomena occur in the cellular immune response: A primary response sets up a pool of activated lymphocytes (in this case, T cells) and generates memory cells that can then mount secondary responses.

a

quickly

with the

differentiate

plasma cells become memory cells primed to respond to subsequent exposures to the same antigen. Should

in the blood rises steeply to higher levels than were achieved in the

humans and many

do not

such

same antigen

specificity.

Responses generated by memory are called secondary responses.

into

titer (concentration)

reach

meeting occur, the memory cells produce more memory cells and larger numbers of effector plasma cells

(Though not indicated in the figure, the production of mature plasma cells takes about 5 days and eight cell gener-

cells

Active and Passive Humoral Immunity

When

your B

encounter antigens and produce antibodies against them, you are exhibiting active cells

humoral immunity nity

is

(

1

or viral

develop

)

(Figure 21.11). Active

naturally acquired infection,

symptoms

(or a lot),

and

immu-

when you get a bacterial may

during which time you of the disease

(2) artificially

receive vaccines. Indeed, once

and

suffer a

acquired it

was

little

when you

realized that

secondary responses are so much more vigorous than primaries, the race was on to develop vaccines to "prime" the immune response by providing a first meeting with the antigen. Most vaccines contain dead or attenuated (living, but extremely weakened) pathogens, or their components. Vaccines provide two benefits:

The Immune System: Innate and Adaptive Body Defenses

Chapter 21

1

Why

is

the secondary response so

much

Why

faster than

Second exposure

O

to antigen

exposure

c

no immunological memory established

in

passive forms of immunity?

the primary response?

c

is

803

—

Secondary immune response to antigen

x, first

Acquired immunity

x

to antigen y

CD

u

c o o



Maintenance of the Body

Principal

Organs of the Respiratory System and

„

Function

Structure

Description, General

Nose

Juttinq external portion supported bone and cartilaqe; by "" ZJ ZJ J internal nasal cavity divided by midline nasal septum

Distinctive Features

and

lined with

Produces mucus; filters, warms, and moistens incoming air; resonance

'

i

chamber

mucosa

Roof of nasal cavity contains olfactory epithelium

speech

for

Receptors for sense of smell

Same

Paranasal sinuses around nasal cavity

as for nasal cavity; also lighten

skull

Passageway connecting nasal cavity to larynx and oral esophagus; three subdivisions: nasopharynx, oropharynx, and laryngopharynx

Pharynx

Passageway

for air

and food

cavity to

Houses

tonsils

(lymphoid tissue masses involved

in

Facilitates exposure of immune system to inhaled antigens

body

protection against pathogens)

Connects pharynx and to trachea; framework of cartilaqe ZJ J dense connective tissue; opening (glottis) can be closed by

Larynx

passageway; prevents food from entering lower respiratory tract

Air

•

1

epiglottis or vocal folds

Houses true vocal cords Trachea

Voice production

and dividing interiorly C-shaped cartilages that are incomplete posteriorly where connected by trachealis muscle

Air

Consists of right and

primary bronchi, which subdivide and tertiary bronchi and bronchioles; bronchiolar walls contain complete layer of smooth muscle; constriction of this muscle impedes expiration

Air

Microscopic chambers at termini of bronchial tree; walls of simple squamous epithelium underlain by thin basement membrane; external surfaces intimately associated with

Main

passageway; cleans, warms, and moistens incoming air

Flexible tube running from larynx into

Bronchial tree

two primary bronchi;

walls contain

left

Alveoli

pulmonary

passageways connecting trachea

with alveoli; cleans, warms, and

within the lungs to form secondary

moistens incoming

sites of

air

gas exchange

capillaries

Reduces surface tension; helps

Special alveolar cells produce surfactant

prevent lung collapse

Lungs

House

Paired composite organs located within pleural cavities of thorax;

composed

primarily of alveoli

and

respiratory passages smaller

than the primary bronchi

respiratory

passageways; stroma

is fibrous elastic connective tissue, allowing lungs to recoil passively during expiration

Pleurae

Serous membranes; parietal pleura

Produce lubricating fluid and compartmentalize lungs

lines thoracic cavity;

visceral pleura covers external lung surfaces

we yell. The power source for creating the airstream is the muscles of the chest, abdomen, and back.

The vocal folds actually produce buzzing sounds. The perceived quality of the voice depends on the coordinated activity of many structures above the glottis. For example, the entire length of the pharynx acts as a resonating chamber, to amplify and enhance the sound quality. The oral, nasal, and sinus cavities also contribute to vocal resonance. In addition, good enunciation depends on the "shaping" of sound into recognizable consonants and vowels by muscles in the pharynx, tongue, soft palate, and lips.

HOMEOSTATIC IMBALANCE Inflammation of the vocal

folds, or laryngitis,

causes

the vocal folds to swell, interfering with their vibra-

This produces a change in the voice tone, hoarseness, or in severe cases inability to speak above a whisper. Laryngitis is also caused by overuse of the tion.

voice, very dry

air,

bacterial infections,

tumors on the

vocal folds, and inhalation of irritating chemicals.

•

Sphincter Functions of the Larynx

Under a

certain conditions, the vocal folds act as sphincter that prevents air passage. During

abdominal straining associated with defecation, the prevent exhalation and the abdominal muscles contract, causing the intra-abdominal pressure to rise. These events, collectively known as Valsalva's maneuver, help empty the rectum and can also splint (stabilize) the body trunk when one lifts a heavy load. glottis closes to

Chapter 22

The Respiratory System

837

Posterior Pseudostratified ciliated

—

columnar

epithelium

cartilage ring

Mucous membrane

Submucosa Adventitia

Anterior (b)

(a)

FIGURE 22.6 (a)

Tissue composition of the tracheal wall.

Cross-sectional view of the trachea, illustrating

its

relationship

to the esophagus, the position of the supporting hyaline

and the trachealis muscle connecting the free ends of the cartilage rings, (b) Photomicrograph of a portion of the tracheal wall (cross-sectional view; 225X). (c) Scanning electron micrograph of cilia in the trachea (1 3,500x). The cilia appear as yellow, grasslike projections. Mucus-secreting goblet cartilage rings,

cells

(orange) with short microvilli are interspersed

between the

ciliated cells.

The Trachea The trachea

windpipe, descends from the larynx through the neck and into the mediastinum. It ends by dividing into the two primary bronchi at midthorax (see Figure 22.1). In humans, it is 10-12 cm (about 4 inches) long and 2.5 cm (1 inch) in diameter, and very flexible and mobile. Interestingly, early anatomists mistook the trachea for a rough-walled artery [trachea = rough). The tracheal wall consists of several layers that are common to many tubular body organs the mu(tra'ke-ah), or

—

cosa,

submucosa, and adventitia (Figure

mucosa has

the

same

22.6).

The

goblet cell-containing pseu-

dostratified epithelium that occurs

throughout most

of the respiratory tract. Its cilia continually propel

debris-laden mucus toward the pharynx. This epithelium rests on a fairly thick lamina propria that has a rich supply of elastic fibers.

HOMEOSTATIC IMBALANCE Smoking inhibits and ultimately destroys cilia, afwhich coughing is the only means of preventing mucus from accumulating in the lungs. For this

ter

(c)

smokers with respiratory congestion should avoid medications that inhibit the cough

reason, reflex.

•

The submucosa,

a connective tissue layer deep

to the mucosa, contains seromucous glands that help produce the mucus "sheets" within the trachea. The outermost adventitia layer is a connective tissue layer reinforced internally by 1 6 to 20 C-shaped rings of hyaline cartilage (Figure 22.6). Because of its elastic elements, the trachea is flexible enough to stretch and move inferiorly during inspiration and recoil during expiration, but the cartilage rings prevent it from collapsing and keep the airway patent despite the pressure changes that occur during breathing. The open posterior parts of the cartilage rings, which abut the esophagus (see Figure 22.6a), are connected by smooth muscle

838

Unit IV

Maintenance of the Body

Trachea

Superior lobe

Superior lobe

of right lung

of left lung

Primary (main) bronchus

Secondary bronchus

(lobar)

Tertiary (segmental)

bronchus

Middle lobe Inferior lobe

Inferior lobe

FIGURE 22.7

Conducting zone passages. The air pathway inferior to the and the primary, secondary, and tertiary bronchi, which

larynx

consists of the trachea

branch into the smaller bronchi and bronchioles

until

the terminal bronchioles of the

lungs are reached.

connective tissue. Because this portion of the tracheal wall is not rigid, the esophagus can expand anteriorly as swallowed food passes through it. Contraction of the trachealis muscle decreases the trachea's diameter, causing expired air to rush upward from the lungs with greater force. This action helps to expel

The Bronchi and Subdivisions: The Bronchial Tree

the trachea when we cough by accelerating the exhaled air to speeds of 100 mph! The last tracheal cartilage is expanded, and a spar of carti-

Conducting Zone Structures The right and left primary (main)

fibers of the trachealis

muscle and by

soft

mucus from

carina (kar-ri'nah; "keel"), projects posteriorly from its inner face, marking the point where the trachea branches into the two primary bronchi. The mucosa of the carina is highly sensitive and violent coughing is triggered when a foreign object makes contact with it. lage, called the

The

Tracheal obstruction

is life

threatening.

Many people

have suffocated after choking on a piece of food that suddenly closed off their trachea. The Heimlich maneuver, a procedure in which air in the victim's lungs is used to "pop out," or expel, an obstructing piece of food, has saved many people from becoming victims of "cafe coronaries." The maneuver is simple to learn and easy to do. However, it is best learned by demonstration because cracked ribs are a distinct possibility when it is done incorrectly. •

is

the site where

way

conducting zone structures give zone structures (Figure 22.8).

to respiratory

bronchi formed by the division of the trachea approximately at the level of T 7 in an erect (standing) person. Each bronchus runs obliquely in the mediastinum before plunging into the medial (brong'ki) are

depression (hilus) of the lung on 22.7).

The

and more

mon

HOMEOSTATIC IMBALANCE

bronchial tree (Figure 22.7)

right

its

primary bronchus than the left and

vertical

own

side (Figure

is

wider, shorter,

is

the

more comto become

an inhaled foreign object By the time incoming air reaches the bronchi, it is warm, cleansed of most impurities, and site for

lodged.

saturated with water vapor.

Once inside the lungs, each primary bronchus subdivides into secondary (lobar) bronchi three on the right and two on the left each supplying one lung lobe. The secondary bronchi branch into thirdorder tertiary (segmental) bronchi, which divide repeatedly into smaller and smaller bronchi (fourth-

—

order, fifth-order, etc.). Overall, there are

—

about 23

orders of branching air passageways in the lungs.

Passages smaller than

1

mm in diameter are called

Chapter 22

FIGURE 22.8

Respiratory zone structures,

The Respiratory System

839

Diagrammatic view of and alveoli, showing the respiratory structures

(a)

respiratory bronchioles, alveolar ducts, alveolar sacs, (b)

Photomicrograph of

a section of

human

lung,

that form the final divisions of the bronchial tree (40x). Notice the thinness of the alveolar walls.

bronchioles ("little bronchi"), and the tiniest of these, the terminal bronchioles, are less than 0.5 in diameter. Because of this branching pattern, the conducting network within the lungs is often called the bronchial or respiratory tree. The tissue composition of the walls of the primary bronchi mimics that of the trachea, but as the conducting tubes become smaller, the following structural changes occur:

mm

Support structures change. The cartilage rings are replaced by irregular plates of cartilage, and by the time the bronchioles are reached, supportive cartilage is no longer present in the tube walls. However, elastic fibers are found in the tube walls throughout the bronchial tree. 1.

Epithelium type changes. The mucosal epithelium thins as it changes from pseudostratified columnar to columnar and then to cuboidal in the 2.

0 840

Unit IV

Maintenance of the Body

terminal bronchioles. Cilia are sparse, and mucus producing cells are absent in the bronchioles. Thus, most airborne debris found at or below the level of the bronchioles is removed by macrophages in the alveoli.

Amount

smooth muscle increases. The relative amount of smooth muscle in the tube walls increases as the passageways become smaller. A complete layer of circular smooth muscle in the bronchioles and the lack of supporting cartilage (which would hinder constriction) allows the bronchioles to 3.

of

provide substantial resistance to air passage under certain conditions (described later).

Respiratory Zone Structures Defined by the presence of thin-walled

air sacs called

=

small cavity), the respiratory zone begins as the terminal bronchioles feed into respiratory bronchioles within the lung (Figure 22.8). Protruding from these smallest bronchioles are scatalveoli (al-ve'o-li; alveol

tered alveoli.

The

alveolar ducts lead into terminal clusters of alveoli

Many

called alveolar sacs. alveoli, the site of gas

people mistakenly equate exchange, with alveolar sacs, but

they are not the same thing. The alveolar sac is analogous to a bunch of grapes, and the alveoli are the indi-

The 300

million or so gas-filled alveoli

lung volume and provide a tremendous surface area for gas exchange. in the lungs account for

most

of the

The Respiratory Membrane The walls of the alveoli are composed primarily of a single layer of squamous epithelial cells, called type I cells, surrounded by a flimsy basal lamina. The thinness of their walls is hard to imagine, but a sheet of tissue

paper

is

much

thicker.

The

alveoli are densely covered

monary

external surfaces of the

with a "cobweb" of pul-

capillaries (Figure 22.9). Together, the alveo-

and capillary walls and their fused basal laminae form the respiratory membrane, an air-blood barrier that has gas on one side and blood flowing past on the other (Figure 22. 9d). Gas exchanges occur readily by simple diffusion across the respiratory membrane 2 passes from the alveolus into the blood, and C0 2 leaves the blood to enter the gasfilled alveolus. The type I cells also are the primary source of angiotensin converting enzyme, which lar

—

plays a role in blood pressure regulation. Scattered

amid the type

form the major part type

I

squamous

cells that

of the alveolar walls are cuboidal

II cells (Figure 22.9c).

The

type

II cells

secrete

a fluid containing surfactant that coats the gas-

exposed

alveolar

is

described later in this chapter.)

The alveoli have three other significant features: They are surrounded by fine elastic fibers of the 1 same type that surround the entire bronchial tree. (2) Open alveolar pores connecting adjacent alveoli (

)

allow air pressure throughout the lung to be equaland provide alternate air routes to any alveoli whose bronchi have collapsed due to disease. (3) Remarkably efficient alveolar macrophages crawl freely along the internal alveolar surfaces. Although ized

huge numbers

of infectious

microorganisms are

continuously carried into the alveoli, alveolar surfaces are usually sterile. Because the alveoli are "dead ends," aged and dead macrophages must be prevented from accumulating in them. Most macrophages simply get swept up by the ciliary current of superior regions and carried passively to the

pharynx. In this manner, we clear and swallow over 2 million alveolar macrophages per hour!

respiratory bronchioles lead into

winding alveolar ducts, whose walls consist of diffusely arranged rings of smooth muscle cells, connective tissue fibers, and outpocketing alveoli. The

vidual grapes.

reducing the surface tension of the alveolar fluid

surfaces.

(Surfactant's

role

in

The Lungs and Pleurae Gross Anatomy of the Lungs

The

paired lungs occupy

all

of the thoracic cavity ex-

which houses the heart, great blood vessels, bronchi, esophagus, and other organs (Figure 22.10). Each cone-shaped lung is suspended in its own pleural cavity and connected to the mediastinum by vascular and bronchial attachments, cept the mediastinum,

collectively called the lung root.

The

anterior, lat-

and posterior lung surfaces lie in close contact with the ribs and form the continuously curving eral,

costal surface. Just deep to the clavicle

is

the apex,

the narrow superior tip of the lung. The concave, inon the diaphragm is the

ferior surface that rests

base.

On

the mediastinal surface of each lung

is

an

which pulmonary enter and leave the lungs.

indentation, the hilus, through

and systemic blood vessels Each primary bronchus also plunges into the hilus on its own side and begins to branch almost immediately. All conducting and respiratory passageways distal to the primary bronchi are found in the lungs. Because the apex of the heart is slightly to the left of the median plane, the two lungs differ slightly in shape and size. The left lung is smaller than the right, and the cardiac notch a concavity in its medial aspect is molded to and accommo-

—

—

The left lung is subdivided into upper and lower lobes by the oblique fissure, whereas the right lung is partitioned into upper, middle, and lower lobes by the oblique and horizontal fissures. Each lobe contains dates the heart (see Figure 22.10a).

number

pyramid-shaped bronchopulmonary segments separated from one another by connective tissue septa. Each segment is served by its own a

of

Chapter 22 What

Type

II

is

the role of surfactant,

(surfactant-

•

produced by the type

Type

I

II

The Respiratory System

841

cells?

cell

of alveolar wall

secreting) cell

Red blood

cell

Capillary

Nucleus type

of

I

(squamous epithelial) cell

of the alveolar epithelium

and the Alveoli (gas-filled

•

airspaces)

Red blood

Alveolar pores

cell

capillary

endothelium

Capillary endothelium-

in capillary

in capillary

(c)

FIGURE 22.9 The respiratory membrane, (a) Scanning electron

W.

micrograph of casts of alveoli and associated pulmonary capillaries

relationship, (c, d) Detailed

(1

R.

100x). From Tissues G. Kessel and

R.

'\\09f\\e 3Lji ui uj/y

the respiratory

and Organs by

H. Kardon.

©

Ajaje/w au}

1979

p

Freeman, (b) Diagrammatic view pulmonary capillary-alveoli

H.

of the

the alveolar (type

uoisudi aoepns

I

cells),

aiji

and the scant basement membranes (fused basal laminae) intervening

anatomy

of

between. Type

membrane composed

of

alveolar cells are also shown.

squamous

epithelial cells

the capillary endothelium,

saonpay

II

(surfactant-secreting)

842

Unit IV

Maintenance of the Body

muscle

Intercostal

Visceral pleura

Thymus

Right superior lobe Horizontal fissure

Right middle lobe

Oblique fissure

Pulmonary

artery

Right inferior lobe

Heart (in

mediastinum

Diaphragm

Base

Left primary

bronchus

of lung

(a)

Pulmonary vein

FIGURE 22.10

Anatomical relationships of organs thoracic cavity, in the (a) Anterior view showing the position of the lungs, which flank mediastinal structures laterally, (b) Photograph of medial aspect of left lung. From A Stereoscopic Atlas of Human Anatomy by David L.

Impression of heart

Oblique fissure

Bassett. (c) Transverse section through the thorax,

showing the lungs, pleural membranes, and major organs present in the mediastinum. (The thymus has been omitted for

Lobules (b)

clarity.)

Vertebra

Posterior

Esophagus (in

posterior mediastinum

Right lung Parietal pleura

Visceral pleura Pleural cavity

Root Right primary

of lung

at hilus

bronchus Left lung

Right pulmonary artery

Thoracic wall

Right pulmonary

Pulmonary trunk

vein Pericardial

membranes Heart

(in

mediastinum)

Anterior mediastinum

Sternum Anterior (c)

Chapter 22

FIGURE 22.11

A

The Respiratory System

843

cast

of the bronchial tree. The individual broncho-

pulmonary segments have been painted different

Right superior lobe ( 3 segments)

Left superior

lobe (4 segments)

colors.

Right middle

lobe (2 segments)

Right inferior lobe (5 segments)

artery

and vein and receives

segmental

(tertiary)

air

from an individual

bronchus. Initially each lung

contains ten bronchopulmonary segments arranged in similar (but not identical) patterns (Figure 22.11), but subsequent fusion of adjacent segmental arteries reduces the number in the left lung to

Left inferior

lobe (5 segments)

and function. Systemic venous blood that is to be oxygenated in the lungs is delivered by the pulmonary arteries, which lie anterior to the pri-

origin,

The bronchopulmonary

mary bronchi (Figure 22.10c). In the lungs, the pulmonary arteries branch profusely along with the bronchi and finally feed into the pulmonary capillary networks surrounding the alveoli (see

segments are clinically important because puldisease is often confined to one or a few segments. Their connective tissue partitions allow diseased segments to be surgically removed without damaging neighboring healthy segments or impair-

Figure 22.9a). Freshly oxygenated blood is conveyed from the respiratory zones of the lungs to the heart by the pulmonary veins, whose tributaries course back to the hilus both with the corresponding bronchi and in the connective

ing their blood supply.

tissue

The smallest subdivisions of the lung visible with the naked eye are the lobules, which appear at the lung surface as hexagons ranging from the size of

segments.

eight or nine segments.

monary

a pencil eraser to the size of a

Each lobule

penny

(Figure 22. 10b).

served by a large bronchiole and its branches. In most city dwellers and in smokers, the connective tissue that separates the individual lobules

is

is

blackened with carbon.

As mentioned

earlier,

the lungs consist largely

The balance

of lung tissue, or its "mattress" or "bed"), is mostly elastic connective tissue. As a result, the lungs are soft, spongy, elastic organs that together weigh just over 1 kg (2.5 pounds). The elasticity of healthy lungs helps to reduce the work of breathing, as de-

of air spaces.

stroma

(literally

scribed shortly.

Blood Supply and Innervation of the Lungs The lungs are perfused by two circulations, the pulmonary and the bronchial, which differ in size,

septa separating the bronchopulmonary

The

large-volume, low-pressure venous blood entering the lungs via the pulmonary arteries contrasts with the small-volume, high-pressure input via the bronchial arteries. The bronchial arteries, which provide systemic blood to lung tissue, arise from the aorta, enter the lungs at the hilus, and then run along the branching bronchi, supplying all lung tissues except the alveoli (these are supplied by the pulmonary circulation). Although some systemic venous blood is drained from the lungs by the tiny bronchial veins, there are multiple anastomoses between the two circulations, and most venous blood returns to the heart via the pulmonary veins.

The

lungs are innervated by parasympathetic and sympathetic motor fibers, and visceral sensory fibers. These nerve fibers enter each lung through the pulmonary plexus on the lung root and run along the bronchial tubes and blood vessels in the

844

Unit IV

Maintenance of the Body

and expiration, the period when

lungs. Parasympathetic fibers constrict the air tubes,

into the lungs,

and sympathetic

gases exit the lungs.

fibers dilate

The Pleurae The pleurae fploo're;

them.

"sides")

form a

layered serosa (see Figure 22.10).

The

thin, double-

layer called the

parietal pleura covers the thoracic wall

and superior

continues around the heart and between the lungs, forming the lateral walls of the mediastinal enclosure and snugly enclosing the lung root. From here, the pleura extends as the layer called the visceral pleura to cover the external lung surface, dipping into and lining its fissures. The pleurae produce pleural fluid, which fills the slitlike pleural cavity between them. This lubricating secretion allows the lungs to glide easily over the thorax wall during our breathing movements. Although the pleurae slide easily across each other, their separation is strongly resisted by the surface tension of the pleural fluid. Consequently, the lungs cling tightly to the thorax wall and are forced to face of the diaphragm.

expand and

It

volume of the increases and decreases

recoil passively as the

racic cavity alternately

The

to describe the breathing important to understand that respiratory pressures are always described relative to atmospheric pressure (P atm ), which is the pressure exerted by the air (gases) surrounding the body. At sea level, atmospheric pressure is 760 Hg (the presit is

mm

mm

sure exerted by a column of mercury 760 high). This pressure can also be expressed in atmosphere units: atmospheric pressure = 760 Hg = 1 atm. A negative respiratory pressure in any respiratory area, such as -4 Hg, indicates that the pressure in that area is lower than atmospheric pressure by 4 Hg (760 - 4 = 756 Hg). A positive respiratory pressure is higher than atmospheric pressure and zero respiratory pressure is equal to atmospheric

mm

mm

mm

mm

Now, we

dur-

relationships that normally exist in the thoracic

are ready to

examine the pressure

cavity.

—

from interfering with another.

It

also limits the

spread of local infections.

Intrapulmonary Pressure

The intrapulmonary

(intra-alveolar) pressure (P pu i) the pressure in the alveoli. Intrapulmonary pressure rises and falls with the phases of breathing, but

is

it

always eventually equalizes with the atmospheric

pressure (Figure 22.12).

Intrapleural Pressure

HOMEOSTATIC IMBALANCE

The

Pleurisy (ploo'rl-se), inflammation of the pleurae, often results from pneumonia. Inflamed pleurae produce less pleural fluid, and the pleural surfaces become dry and rough, resulting in friction and stabbing pain with each breath. Conversely, the pleurae may produce an excessive amount of fluid, which exerts pressure on the lungs. This type of pleurisy hinders breathing movements, but it is much less painful than the dry rubbing type. Other fluids that may accumulate in the pleural cavity include blood (leakage from damaged blood vessels) and blood filtrate (the watery fluid that oozes from the lung capillaries when right- sided heart failure occurs). The general term for this type of fluid accumulation in the pleural space is pleural effusion.

we can begin

pressure.

pleurae also help divide the thoracic cavity chambers the central mediastinum and the two lateral pleural compartments, each containing a lung. This compartmentalization helps prevent one mobile organ (for example, the lung or heart)

*^(J(^

Before

process,

tho-

ing breathing. into three

Pressure Relationships in the Thoracic Cavity

•

pressure in the pleural cavity, the intrapleural pressure (Pi P ), also fluctuates with breathing phases.

mm

However, it is always about 4 Hg less than Ppul Hence, P ip is negative relative to both the intrapulmonary and atmospheric pressures. The question often asked is "How is this nega.

tive intrapleural pressure established?" or

"What

causes it?" Let's examine the forces that exist in the thorax to see if we can answer these questions. First of

all,

we know there

are opposing forces acting.

forces act to pull the lungs (visceral pleura)

from the thorax wall

(parietal pleura)

Two

away

and cause lung

collapse: 1.

The

lungs' natural tendency to recoil. Because assume the smallest

of their elasticity, lungs always size possible. 2.

The

surface tension of the alveolar fluid.

The

surface tension of the alveolar fluid constantly acts to

Mechanics of Breathing

draw the

alveoli to their smallest possible

dimen-

sion.

Breathing, or pulmonary ventilation, consists of

two phases: inspiration, the period when

air

flows

However, these lung-collapsing forces are opposed by the natural elasticity of the chest wall, a force that

Chapter 22

The Respiratory System

845

Atmospheric pressure

tends to pull the thorax outward and to enlarge the lungs.

So which force wins? The answer is neither in a healthy person, because of the strong adhesive force between the parietal and visceral pleura. Pleural fluid secures the pleurae together in the

same way

a

drop of water holds two glass slides together. The pleurae slide from side to side easily but they remain closely apposed, and separating them requires extreme force. The net result of the dynamic interplay

between these forces ity

P ip

is

a negative

P ip

Lung Thoracic wall Parietal

pleura Pleural cavity

.

The amount of pleural fluid in the pleural cavmust remain minimal in order for the negative to be maintained. Active pumping of the

Visceral

pleura

pleural fluid out of the pleural cavity into the lym-

phatics occurs almost continuously. If it didn't, fluid would accumulate in the intrapleural space (remember, fluids move from high to low pressure), producing a positive pressure in the pleural cavity.

The importance

760

mm

Hg

(0

mm

Hg)

FIGURE 22.12 Intrapulmonary and intrapleural pressure relationships. Differences in pressure relative to atmospheric pressure (760 mm Hg) are given in parentheses.

of negative pressure in the in-

and the tight coupling of the lungs thorax wall cannot be overemphasized. Any condition that equalizes P ip with the intrapulmonary (or atmospheric) pressure causes immediate lung collapse. It is the transpulmonary pressure the difference between the intrapulmonary and intrapleural pressures (P pu - P ip that keeps the air spaces of the lungs open or, phrased another way, keeps the lungs from collapsing. trapleural space to the

:

—

\

i

)

—

changes, and pressure changes lead to the flow of gases to equalize the pressure. The relationship between the pressure and volume of a gas is given by Boyle's law: At constant temperature, the pressure of a gas varies inversely

with

its

volume. That

is:

P V = P 2 V2 X

where P

HOMEOSTATIC IMBALANCE

mercury,

com-

Atelectasis (at"e-lik'tah-sis), or lung collapse,

monly occurs when air enters the pleural cavity through a chest wound, but it may result from a rupture of the visceral pleura, which allows air to enter the pleural cavity from the respiratory tract.

It is

a

common The ferred

sequel to pneumonia. presence of air in the intrapleural space

to

as

"air thorax").

is re-

a pneumothorax (nu"mo-tho'raks The condition is reversed by closing ;

the "hole" and drawing air out of the intrapleural

space with chest tubes, which allows the lung to reinflate

and resume

its

normal function. Note that be-

cause the lungs are in separate cavities, one lung can collapse without interfering with the function of the other.

•

the pressure of the gas in millimeters of

is

V

subscripts

X

is its

1

volume

and and resulting

in cubic millimeters,

and 2 represent the

initial

conditions respectively.

Gases always

fill

their container. Therefore, in

a large container, the of gas will be far apart

molecules in a given amount

and the pressure

will be low.

But if the volume of the container is reduced, the gas molecules will be forced closer together and the pressure will rise. A good example is an inflated automobile tire. The tire is hard and strong enough to bear the weight of the car because air is compressed to about one-third of its atmospheric volume in the tire, providing the high pressure. Now let us see how this relates to inspiration and

expiration.

Inspiration Visualize the thoracic cavity as a gas-filled box with

Pulmonary Ventilation: Inspiration and Expiration Pulmonary ventilation is a mechanical process that depends on volume changes in the thoracic cavity. A rule to keep in

cussion

is

that

mind throughout the following disvolume changes lead to pressure

a single entrance at the top, the tubelike trachea.

The volume

box

changeable and can be increased by enlarging all of its dimensions, thereby decreasing the gas pressure inside it. This drop in pressure causes air to rush into the box from the atmosphere, because gases always flow down their of this

pressure gradients.

is

846

Maintenance of the Body

Unit IV

Sequence

(T) Inspiratory

Changes

in anterior-posterior and superior-inferior dimensions

of events

Changes

in lateral

dimensions

muscles

contract (diaphragm

descends;

rib

cage

rises)

Ribs elevated

Y

and sternum

(5) Thoracic cavity

flares

volume increases

as

external intercostals

© c

contract

Lungs stretched; intrapulmonary

o

volume increases

CL

i \

(4) Intrapulmonary

C

pressure drops (to -1 Hg)

mm

J

(5) Air (gases) flows

lungs down its pressure gradient until intrapulmonary pressure is 0 (equal into

Diaphragm moves interiorly

during

contraction

atmospheric

to

pressure)

©Inspiratory muscles relax (diaphragm rises; rib cage descends due to recoil of costal cartilages)

©Thoracic

Ribs and sternum depressed as

cavity

volume decreases

external intercostals

\ c

relax

(3) Elastic lungs recoil

o

passively; intrapul-

monary volume decreases

Q.

X ID

\ (?) Intrapulmonary

pressure rises (to +1 Hg)

mm

(5) Air (gases) flows

out of lungs

Diaphragm

down

moves

pressure gradient intrapulmonary pressure is 0 its

superiorly

until

FIGURE

Changes

22.1 3

volume during

in

as

thoracic

inspiration (top)

and

expiration (bottom). The sequence of

column includes flowcharts indicating volume changes during inspiration and expiration. The events

in

the

left

lateral

views

in

the middle column

how

contract and

relax).

The superior views

external intercostal muscles alternately

external intercostal muscles.

quiet

the inspiratory muscles

di-

acti-

vated. Here's

show

of transverse thoracic sections

— the aphragm and external intercostal muscles — are when

relaxes

changes in the superior-inferior dimension (as the diaphragm alternately contracts and relaxes) and in the anterior-posterior dimension (as the

The same thing happens during normal

inspiration,

it

quiet inspiration works:

in

the

right column show lateral dimension changes resulting from alternate contraction and relaxation of the

Action of the diaphragm. When the domeshaped diaphragm contracts, it moves inferiorly and 1.

flattens out (Figure 22.13, top).

superior-inferior

cavity increases.

dimension

As

a result, the

(height) of the thoracic

.

Chapter 22

Action of the intercostal muscles. Contraction of the external intercostal muscles lifts the rib cage and pulls the sternum superiorly (Figure 22.13, top). Because the ribs curve downward as well as forward around the chest wall, the broadest lateral and anteroposterior dimensions of the rib cage are normally directed obliquely downward. But when the ribs are raised and drawn together, they swing outward, expanding the diameter of the thorax both laterally and in the anteroposterior plane. This is much like the action that occurs when a curved bucket handle 2.

is

As thoracic volume

9

Volume

1

increases.

As

mm Hg relative to Patm

pulmonary pressure

< Patm

is

less

a result, .

),

breath

Expiration

r- Intrapulmonary

cn

I

+2

k

E

£

o

3

\

— Trans-

in CD

/

pulmonary

Q.

pressure

O

i /

f

"i

tu

CL

x

C/3

O E Q.

CD

Intrapleural

pressure

-8

P pu drops i

Anytime the

intra-

than the atmospheric

rushes into the lungs along the pressure gradient. Inspiration ends when P pul = P atm During the same period, P ip declines to about pressure (Ppul

what happens to the

4 seconds elapsed

—

about

of

Inspiration

monary volume

increases,

847

intrapulmonary pressure? To the intrapleural pressure?

raised.

Although these actions expand the thoracic dimensions by only a few millimeters along each plane, this is enough to increase thoracic volume by almost 500 ml the usual volume of air that enters the lungs during a normal quiet inspiration. Of the two types of inspiratory muscles, the diaphragm is far more important in producing the volume changes that lead to normal quiet inspiration. As the ^horacic dimensions increase during inspiration, the lungs are stretched and the intrapul-

The Respiratory System

air

FIGURE 22.14

Changes

in

intrapulmonary and

intrapleural pressures during inspiration and

expiration. Notice that normal atmospheric pressure (760

mm

Hg)

is

given a value of 0 on the scale.

.

-6

mm Hg relative to Patm (Figure 22.14).

During the deep or forced inspirations that occur during vigorous exercise and in some chronic obstructive pulmonary diseases, the thoracic volume is further increased by activity of accessory muscles. Several muscles, including the scalenes and sternocleidomastoid muscles of the neck and the pectoralis minor of the chest, raise the ribs even more than occurs during quiet inspiration. Additionally, the back extends as the thoracic curvature is straightened by

The

internal intercostal muscles

may

also help to

depress the rib cage and decrease thoracic volume. Control of accessory muscles of expiration is important when precise regulation of air flow from the lungs is desired. For instance, the ability of a trained

on the coordinated activity of several muscles normally used in

vocalist to hold a musical note depends

forced expiration.

the erector spinae muscles.

Physical Factors Influencing Expiration

Pulmonary Ventilation

Quiet expiration in healthy individuals is a passive more on lung elasticity than on muscle contraction. As the inspiratory muscles relax and resume their resting length, the rib cage descends and the lungs recoil. Thus, both the thoracic and intrapulmonary volumes decrease. This volume decrease compresses the alveoli, and P pul rises to about 1 Hg above atmospheric pressure (see Figprocess that depends

mm

When Ppu] > P atm the pressure gradient forces gases to flow out of the lungs.

ure 22.14).

,

an active process produced by contraction of abdominal wall muscles, primarily the oblique and transversus muscles. These contracForced expiration

is

increase the intra-abdominal pressure, which forces the abdominal organs superiorly against the diaphragm, and (2) depress the rib cage. tions

(1)

As we have seen, the lungs are stretched during inspiration and recoil passively during expiration. The inspiratory muscles consume energy to enEnergy is also used to overcome various factors that hinder air passage and pullarge the thorax.

monary

ventilation.

These

factors are

examined

next.

Airway Resistance The major nonelastic is friction,

source of resistance to gas flow

or drag, encountered in the respiratory

passageways.

The

relationship between gas flow

(F),

848

Unit IV

Maintenance of the Body

Hence, as shown in Figure 22.15, the greatest tance to gas flow occurs in the

^(J)^

resis-

medium- sized bronchi.

HOMEOSTATIC IMBALANCE

Smooth muscle

of

the bronchiolar walls

is

ex-

and certain chemicals. For example, inhaled irritants and inflammatory chemicals such as histamine activate a quisitely sensitive to neural controls

reflex of the

parasympathetic division of the nervous

system that causes vigorous constriction of the bronchioles and dramatically reduces air passage.

1

10

5

20

15

Indeed, the strong bronchoconstriction occurring during an acute asthma attack can stop pulmonary ventilation almost completely, regardless of the pres-

23

sure gradient. Conversely, epinephrine released during sympathetic nervous system activation or

Airway generation (stage of branching)

FIGURE 22.15 Resistance in respiratory passageways. Airway resistance peaks in the medium-sized bronchi and then declines sharply as the total cross-sectional area of the airway increases rapidly.

pressure (P), and resistance (R) lowing equation:

is

given by the

fol-

administered as a drug dilates bronchioles and reduces airway resistance. Local accumulations of

mucus, infectious material, or

lation to life-sustaining levels.

Notice that the factors determining gas flow in the respiratory passages and blood flow in the cardiovascular system are equivalent.

The amount of gas

ing into and out of the alveoli

is

flow-

directly proportional

to AP, the difference in pressure, or the pressure

between the external atmosphere and the alveoli. Normally very small differences in pressure produce large changes in the volume of gas flow. The average pressure gradient during normal quiet breathing is 2 Hg or less, and yet it is sufficient to move 500 ml of air in and out of the lungs with gradient,

mm

each breath. But, as the equation also indicates, gas flow changes inversely with resistance. That is, gas flow decreases as resistance due to friction increases. As with the cardiovascular system, resistance in the respiratory tree is determined mostly by the diameters of the conducting tubes. However, as a rule, airway resistance is insignificant for two reasons: part of the conduct-

Airway diameters in the first ing zone are huge, relatively speaking. 1

.

Gas flow stops

the terminal bronchioles (where small airway diameters might start to be a problem) and diffusion takes over as the main force 2.

driving gas

at

movement.

solid

tumors in the

passageways are important sources of airway resistance in those with respiratory disease. Whenever airway resistance rises, breathing movements become more strenuous, but such compensation has its limits. When the bronchioles are severely constricted or obstructed, even the most magnificent respiratory efforts cannot restore venti-

•

Alveolar Surface Tension Forces At any gas-liquid boundary, the molecules of the liquid are more strongly attracted to each other than to the gas molecules. This unequal attraction produces a state of tension at the liquid surface, called surface tension, that (1) draws the liquid molecules closer together and reduces their contact with the dissimilar gas molecules, and (2) resists any force that tends to increase the surface area of the liquid.

molecules and has a very high surface tension. Because water is the

Water

is

composed

of highly polar

major component of the liquid film that coats the it is always acting to reduce the alvesmallest possible size. If the film was pure water, the alveoli would collapse between breaths. But the alveolar film contains surfactant

alveolar walls,

oli to their

(ser-fak'tant), a detergent-like

proteins produced by the type

complex II

of lipids

and

alveolar cells. Sur-

factant decreases the cohesiveness of water molecules,

much

the

way

a laundry detergent reduces the

attraction of water for water, allowing water to interact

with and pass through

fabric.

As

a result, the

is reduced, and energy is needed to overcome those forces to expand the lungs and discourage alveolar collapse.

surface tension of alveolar fluid

less

Chapter 22

The Respiratory System

According to some authorities, breaths that are deeper than normal stimulate type II cells to secrete

fluid or thick

more

bronchitis, respectively)

surfactant.

^(J|^

When

HOMEOSTATIC IMBALANCE

too

2.

Block the smaller respiratory passages

surfactant

is

present, surface tension

can collapse the alveoli. Once this happens, the alveoli must be completely reinflated during each inspiration, an effort that uses tremendous amounts of energy. This is the problem faced by newborns with infant respiratory distress syndrome (IRDS), a condition peculiar to premature babies. Since inadequate pulmonary surfactant is produced until the last two months of fetal development, babies born prematurely often are unable to keep their alveoli inflated between breaths. IRDS is treated with posiforces

Reduce the production of surfactant

4.

Decrease the

tive-pressure respirators that force air into the alve-

keeping them open between breaths. Spraying natural or synthetic surfactant into the newborn's respiratory passageways also helps. Many IRDS survivors suffer from bronchopulmonary dysplasia, a chronic lung disease, during childhood and beyond. This condition is believed to result from inflammatory injury to respiratory zone structures caused by use of the respirator on the newborn's delicate lungs. • oli,

Healthy lungs are unbelievably stretchy, and this distensibility is referred to as lung compliance. Specifically, lung compliance (Cj is a measure of the change in lung volume (AVL that occurs with a given change in the transpulmonary pressure [A(Ppu] - P ip )]. This is stated as )

AVL ~ A(Ppul - Pip

L

its

the lung compliance, the

more energy

is

just to breathe.

Deformities of the thorax, ossification of the costal cartilages (common during old age), and paralysis of the intercostal muscles all reduce lung compliance by hindering thoracic expansion. •

Respiratory Volumes and Pulmonary Function Tests The amount

of air flushed in

and out

of the lungs de-

pends on the conditions of inspiration and expiration. Consequently, several respiratory volumes can be described. Specific combinations of these respiratory volumes, called respiratory capacities, are measured to gain information about a person's respiratory status.

The

four respiratory

determined largely by two factors: (1) distensibility of the lung tissue and of the surrounding thoracic cage, and (2) alveolar surface tension. Because lung (and thoracic) distensibility is generally high and alveolar surface tension is kept low by surfactant, the lungs of healthy people tend to have high compliance, which favors efficient ventilation. Compliance is diminished by factors with any of is

the following effects:

Reduce the natural resilience of the lungs, such (e.g., development of nonelastic scar tis-

of interest are tidal,

The

values recorded in Figure 22.16a represent norfor a healthy 20-year-old male weighing about 70 kg (155 pounds). Figure 22.16b provides

mal values

average values for males and females. During normal quiet breathing, about 500 ml of air moves into and then out of the lungs with each breath. This respiratory

another way, the higher the lung compliance, the easier it is to expand the lungs at any given transpul-

monary pressure. Lung compliance

volumes

inspiratory reserve, expiratory reserve, and residual.

)

The more a lung expands for a given rise in transpulmonary pressure, the greater its compliance. Said

sue in tuberculosis)

cage or

^J)^ HOMEOSTATIC IMBALANCE

(TV).

1.

flexibility of the thoracic

Respiratory Volumes

Lung Compliance

as fibrosis

with

expand

The lower needed

(e.g.,

mucus, as in pneumonia or chronic

3.

ability to little

849

The amount

beyond the

tidal

volume

is

the tidal

volume

can be inspired forcibly volume (2100 to 3200 ml) is called of air that

volume (IRV). The expiratory reserve volume (ERV) amount of air normally 1000 to 1200 ml

the inspiratory reserve

—

is

the

— that

can be evacuated from the lungs after a tidal expiration. Even after the most strenuous expiration, about 1 200 ml of air remains in the lungs; this is the residual volume (RV), which helps to keep the alveoli patent (open) and to prevent lung collapse.

Respiratory Capacities

The

respiratory capacities include inspiratory capacity, functional residual capacity, vital capacity, and total lung capacity (Figure 22.16). As noted, the respiratory capacities always consist of two or more

lung volumes.

850

Unit IV

Maintenance of the Body

6000

5000 Inspiratory

reserve volume 3100 ml

Inspiratory capacity

4000

3600 ml capacity

Vital

4800 ml

I en

I

3000

Total Tidal

lung

volume 500 ml

capacity 6000 ml

Expiratory reserve volume 1200 ml

2000

Functional residual capacity

1000

2400 ml

Residual volume 1200 ml 0 (a)

Spirographic record for a male

Adult male average value

Adult female average value

Description

500 ml

500 ml

Amount

3100 ml

1900 ml

1200 ml

700 ml

Residual volume (RV)

1200 ml

1100 ml

Total lung capacity (TLC)

6000 ml

4200 ml

Measurement

Tidal

volume (TV)

Inspiratory reserve

volume (IRV)

of air inhaled or

Amount

of air that

volume

inhalation

Amount

of air that

exhaled with each breath under resting conditions

can be

forcefully inhaled after

can be

forcefully

a normal

tidal

o re

Expiratory reserve

volume (ERV)

exhaled

after a

normal

tidal

volume exhalation

in a>

Amount

(A

of air remaining in the lungs after

Maximum amount of air contained in TLC = TV + IRV + ERV + RV

a forced exhalation

lungs after a

maximum

inspiratory

effort:

O re

c re

u

Vital

capacity (VC)

4800 ml

Maximum amount of air that can be expired after a maximum VC = TV + IRV + ERV (should be 80% TLC)

3100 ml

>.

o re

Inspiratory capacity (IC)

3600 ml

2400 ml

Functional residual capacity (FRC)

2400 ml

1800 ml

inspiratory

effort:

Maximum amount IC = TV + IRV

of air that

can be inspired

after

a normal expiration:

'5. in

o cc

(b)

Summary

of respiratory

FIGURE 22.16

volumes and capacities

The amount

FRC

volumes and capacities

for

in

=

of air

ERV

remaining

+

in

the lungs after a normal

tidal

volume

expiration:

RV

males and females

Respiratory volumes and capacities,

spirographic record of respiratory volumes, (b) Respiratory

for

Volume

a healthy

(a) Idealized

young 70-kg adult male,

males and females.

inspiratory capacity (IC) is the total of air that can be inspired after a tidal expiration; thus, it is the sum of TV and IRV. The functional residual capacity (FRC) is the combined RV and ERV and represents the amount of air remaining in the lungs after a tidal expiration. Vital capacity (VC) is the total amount of exchangeable air. It is the sum of TV IRV and ERV In healthy young males, VC is approximately 4800 ml. The total lung capacity (TLC) is the sum of all lung volumes and is normally around 6000 ml in males. As indicated in Figure 22.16b, lung volumes and capacities (with the possible exception of TV) tend to

be smaller in women than in women's smaller size.

men

because of

Dead Space Some

of the inspired air

fills

the conducting respira-

and never contributes to gas exchange in the alveoli. The volume of these conducting zone conduits, which make up the anatomical dead space, typically amounts to about 1 50 ml. (The rule of thumb is that the anatomical dead space tory passageways

volume in a healthy young adult is equal to pound of body weight.) This means that 500 ml, only 350 ml of it is involved in

1

if

ml

per

TV

is

alveolar

n

The Respiratory System

Chapter 22

TABLE 22.2

/

Effects of Breathing Rate

851

and Depth on Alveolar Ventilation

of Three Hypothetical Patients Breathing

%

Pattern of

Hypothetical

Dead Space

Tidal

Patient

Volume (DSV)

(TV)

— Normal rate and depth — Slow, deep breathing — Rapid, shallow breathing

Volume

of

TV =

Respiratory

Minute

Alveolar

Dead Space

Rate'

Ventilation

Ventilation

Volume

50 ml

500 ml

20/min

10,000 ml/min

7000 ml/mi

30%

II

150 ml

1000 ml

10/min

10,000 ml/min

8500 ml/min

15%

III

1

50 ml

250 ml

40/min

10,000 ml/min

4000 ml/min

60%

I

*Respiratory rate values are

ventilation.

breath

is

artificially

1

adjusted to provide equivalent minute respiratory volumes as a baseline for comparison of alveolar ventilation.

The remaining 150 ml

of the tidal

in the anatomical dead space.

some

exchange (due to alveolar collapse or obstruction by mucus, for example), the alveolar dead space is added to the anatomical dead space, and the sum of the nonuseful volumes is referred to as total dead space. If

alveoli cease to act in gas

Pulmonary Function Tests Because the various lung volumes and capacities are often abnormal in people with pulmonary disorders, they are routinely measured in such patients. The measuring device, a spirometer (spirom'e-ter), is a simple instrument utilizing a hollow bell inverted over water. The bell moves as the patient breathes into a connecting mouthpiece, and a graphic recording is made on a rotating drum. Spirometry is most useful for evaluating losses in respiratory function and for following the course of certain respiratory diseases. Although it cannot provide a specific diagnosis, it can distinguish between obstructive pulmonary disease involving increased airway resistance (such as chronic bronchitis) and restrictive disorders involving a reduction in total lung capacity resulting from structural or functional changes in the lungs (due to diseases such as tuberculosis, or to fibrosis due to exposure to certain environmental agents such as asbestos). Increases in TLC, FRC, and RV may occur as a result of hyperinflation of the lungs in obstructive disease, whereas VC, TLC, FRC, and RV are reduced in restrictive diseases, which limit lung expansion. More information can be obtained about a patient's ventilation status by assessing the rate at which gas moves into and out of the lungs. The minute ventilation is the total amount of gas that flows into or out of the respiratory tract in 1 minute. During normal quiet breathing, the minute ventilation in healthy people is about 6 L/min (500 ml per breath multiplied by 12 breaths per minute). During

vigorous exercise, the minute ventilation may reach 200 L/min. Two other useful tests are FVC and FEV. FVC, or forced vital capacity, measures the amount of gas expelled when a subject takes a deep breath and then forcefully exhales maximally and as rapidly as possible. FEy or forced expiratory volume, determines the amount of air expelled during specific time intervals of the FVC test. For example, the volume exhaled during the first second is FEV^ Those with healthy lungs can exhale about 80% of the FVC within 1 second. Those with obstructive pulmonary disease have a low

FEV 1; and

restrictive disease pro-

duces a low FVC.

Alveolar Ventilation Minute ventilation values provide

a rough yardstick

but the alveolar ventilation rate (AVR) is a better index of effective ventilation. The AVR takes into account the volume of air wasted in the dead space and measures the flow of fresh gases in and out of the alveoli during a particular time interval. AVR is computed with this equation: for assessing respiratory efficiency,

AVR (ml/mm)

=

frequency

x

(TV - dead

(breaths/min)

space)

(ml/breath)

In healthy people, AVR is usually about 12 breaths per minute times the difference of 500 - 1 50 ml per breath, or 4200 ml/min. Because anatomical dead space is constant in a particular individual, increasing the

volume

of each

AVR

and gas

inspiration (breathing depth) enhances

exchange more than raising the respiratory

rate.

AVR drops

dramatically during rapid shallow breathing because most of the inspired air never reaches the exchange sites. Furthermore, as tidal volume approaches the dead space value, effective ventilation

approaches zero, regardless of how fast a person is breathing. The effects of breathing rate and breathing depth on alveolar ventilation are summarized for three hypothetical patients in Table 22.2.

— Unit IV

TABLE

22.3

z

Maintenance of the Body

Nonrespiratory Air (Gas) Movements

Movement

Mechanism and Result

Cough

Taking a deep breath, closing glottis, and forcing air superiorly from lungs against glottis; glottis opens suddenly and a blast of air rushes upward; can dislodge foreign particles or mucus from lower respiratory tract and propel such substances superiorly

Sneeze

Similar to a cough, except that expelled air is directed through nasal cavities as well as through oral cavity; depressed uvula closes oral cavity off from pharynx and routes air upward through nasal cavities; sneezes clear upper respiratory passages

Crying

Inspiration followed by release of air n a

number of short

expirations; primarily an emotionally induced

mechanism

same

movements produced;

Laughing

Essentially

Hiccups

Sudden inspirations resulting from spasms of diaphragm; believed to be initiated by irritation of diaphragm or phrenic nerves, which serve diaphragm; sound occurs when inspired air hits vocal folds of closed glottis

Yawn

Very

as crying

in

terms of

air

also an emotionally induced response

deep inspiration, taken with jaws wide open; formerly believed to be triggered by need to increase amount of oxygen in blood but this theory is now being questioned; ventilates all alveoli (not the case in normal quiet breathing)

Nonrespiratory Air Movements Many

move

processes other than hrea thin g

or out of the lungs, and these processes

air into

may modify

the normal respiratory rhythm. Most of these nonrespiratory air movements result from reflex activity,

most

but some are produced voluntarily. The

common

of these

movements

are described in

Table 22.3.

Basic Properties of Gases Gas exchange

in the body occurs by bulk flow of and solutions of gases and by diffusion of gases through tissues. To understand these processes, we must examine some of the physical properties of gases and their behavior in liquids. Two more gas laws Dolton's low of partial pressures and Henry's law provide most of the information we

gases

I

(

—

need.

Dalton's

Law

of Partial Pressures

each gas

—

its

partial pressure

—

is

directly propor-

tional to the percentage of that gas in the gas

mixture. As indicated in Table 22.4, nitrogen makes up about 7Q% of air, and the partial pressure of nitrogen P N is ^8.6% x 760 Hg, or 597 Hg. Oxygen gas, which accounts for nearly 21% of the .

mm

mm

mm

influenced by gravity, partial pressures decline in direct proportion to the decrease in atmospheric pressure. For example, at 10,000 feet above sea level

where the atmospheric pressure

mm

is 563 Hg, P Q ^ 110 Hg. Moving in the opposite direction" atmospheric pressure increases by 1 atm 7 60 Hg) for each 33 feet of descent (in water below sea level. Thus, at 99 feet below sea level, the total pressure exerted on the body is equivalent to 4 atm, or 3040 Hg, and the partial pressure exerted by each component gas is also quadrupled. is

mm

(

mm

I

mm

Henry's

Law

According

to

is

Dal ton's law of partial pressures states that the total pressure exerted by a mixture of gases is the sum of the pressures exerted independently by each gas in the mixture. Further, the pressure exerted by

mm

atmosphere, has a partial pressure (PoJ of 159 (20.9% x 760 Hg). Thus, nitrogen and oxygen together contribute about 99% of the total atmospheric pressure. Air also contains 0.04% carbon dioxide, up to 0.5% water vapor, and insignificant amounts of inert gases (such as argon and helium'. At high altitudes, where the atmosphere is less

Hg

Henry's law, when a mixture

of gases

in contact with a liquid, each gas will dissolve in

the liquid in proportion to its partial pressure. Thus the greater the concentration of a particular gas in the gas phase, the more and the faster that gas will go into solution in the liquid. At equilibrium, the gas partial pressures in the two phases are the same. If, however, the partial pressure of one of the gases later becomes greater in the liquid than in the adjacent gas phase, some of the dissolved gas molecules will reenter the gaseous phase. So the direction and amount of movement of each gas is determined by its partial pressure in

Chapter 22

TABLE 22.4

Comparison of Gas and in the Alveoli

Partial Pressures

Atmosphere (Sea

The Respiratory System

and Approximate Percentages

in

the Atmosphere

Alveoli

Level)

Partial

Gas

Partial

Approximate

Pressure

Approximate

Pressure

Percentage

(mm Hg)

Percentage

(mm Hg)

N2

78.6

597

74.9

569

o2 C0 2 H 20

20.9

159

13.7

104

0.04

0.3

5.2

40

0.46

3.7

6.2

47

100.0%

760

760

100.0%

the two phases. This flexible situation

what occurs and

when

is

exactly

gases are exchanged in the lungs

of a gas will dissolve in a liquid at

any given partial pressure also depends on the solubility of the gas in the liquid and on the temperature of the liquid. The gases in air have very different solubilities in water (and in plasma). Car-

bon dioxide soluble as at a

02

is

most

C0 2

,

soluble.

and

N2

is

given partial pressure,

dissolves in water,

into solution.

temperature club soda,

is

The

Oxygen

is

only 1/20 as

nearly insoluble. Thus,

much more C0 2 than

and practically no

high

02

is

2

goes

is greater than 2.5-3 atm. Excessively concentrations generate huge amounts of

free radicals, resulting in

turbances, coma, and death.

profound

CNS dis-

•

Composition of Alveolar Gas As shown

in Table 22.4, the gaseous

makeup

of the

atmosphere is quite different from that in the alveThe atmosphere is almost entirely 0 2 and N 2; the alveoli contain more C0 2 and water vapor and much less 0 2 These differences reflect the effects of: (1) gas exchanges occurring in the lungs (0 2 diffuses from the alveoli into the pulmonary blood and C0 2 diffuses in the opposite direction), (2) humidification of air by conducting passages, and (3) the mixing of alveolar gas that occurs with each breath. Because only 500 ml of air is inspired with each tidal inspiration, gas in the alveoli is actually a mixture of newly inspired gases and gases remaining in the respiratory passageways between oli.

.

to decrease gas solubility.

which

N

effect of increasing the liquid's

produced by forcing

Think

of

C0 2 gas to

you take club soda and al-

dissolve in water under high pressure.

If

the cap off a refrigerated bottle of low it to stand at room temperature, in just a few minutes you will have plain water all the 2 gas will have escaped from solution. Hyperbaric oxygen chambers provide clinical applications of Henry's law. These chambers contain 0 2 gas at pressures higher than 1 atm and are used to force greater-than-normal amounts of 2 into the blood of patients suffering from carbon monoxide poisoning, circulatory shock, or asphyxiation. Hyperbaric therapy is also used to treat individuals with gas gangrene or tetanus poisoning because the anaerobic bacteria causing these infections cannot live in the presence of high 0 2 levels. Scuba diving provides another illustration of Henry's law (see A Closer Look on p. 866).

—

C0

0

*^J)^

when P Qi harmful

tissues.

How much

853

HOMEOSTATIC IMBALANCE

Although breathing 0 2 gas at 2 atm is not a problem for short periods, oxygen toxicity develops rapidly

breaths.

The partial pressures of 0 2 and C0 2 are easily changed by increasing breathing depth and rate. A high

AVR brings more 0 2 into the

alveolar

alveoli, increasing

P Qv and rapidly eliminates

C0 2

from the

lungs.

Gas Exchanges Between the Blood, Lungs, and Tissues As

described, during external respiration oxygen en-

and carbon dioxide leaves the blood in the lungs. At the body tissues, where the process is called ters

same gases move in opposite by the same mechanism (diffusion).

internal respiration, the directions

854

Maintenance of the Body

Unit IV

Inspired

Expired

air:

P 02 1 60 P C02 0.3

mmHg mm Hg

150

air:

120mmHg

P 0z P C02

27

mmHg

/

100

o 2 co 2 50

P 02 1 04

mm

Hg

External respiration

Blood leaving alveolar capillaries:

Blood entering

P 02 P C02

alveolar capillaries

p co2 45

mm

1

04 40

so

mmHg mm Hg

0.25

Time

veins

the

t End of

capillary

capillary

pulmonary

FIGURE 22.18 Pulmonary

in

0.75

Start of

t

H9

0.50

pulmonary

capillary (s)

Oxygenation of blood

capillaries.

Note

in

the

that the time from blood

entering the pulmonary capillaries (indicated by

Po 2

Pulmonary

is

104

mm

Hg

0) until

the

approximately 0.25 second.

is

arteries

by systemic arteries to all body tissues. Although this color change is due to 0 2 uptake and binding to hemoglobin in red blood cells (RBCs), C0 2 exchange (unloading) is occurdistribution

Systemic

Systemic

veins

arteries

ring equally fast.

Blood leaving

Blood entering tissue capillaries:

tissue capillaries:

40 45

P 02 P C02

mm mm

Hg Hg

P 02 P Co2

1

04 40

mmHg mm Hg

Three factors influencing the movement of oxygen and carbon dioxide across the respiratory membrane are: 1

.

2.

o 2 co 2 o 2 co 2 Internal

Matching

and gas

of alveolar ventilation

solubilities

and pulmonary

blood perfusion 3.

respiration

Partial pressure gradients

Structural characteristics of the respiratory

mem-

brane Tissues: less than 40 mm Hg P COs greater than 45 mm Hg

Po 2

Partial Pressure

Gradients

and Gas Solubilities o 2 co 2

FIGURE 22.17 Partial pressure gradients promoting gas movements in the body. Top: Gradients promoting 0 2 and C0 2 exchange across the respiratory membrane in the lungs. Bottom: Gradients promoting gas movements across systemic capillary membranes in body tissues. (Note that the composition of alveolar air and expired air are different. This is because some dead space air mixes with the

air

being expired.)

External Respiration:

Pulmonary Gas Exchange During external respiration, dark red blood flowing through the pulmonary circuit is transformed into the scarlet river that

is

returned to the heart for

Because the P Ql of venous blood in the pulmonary arteries is only 40 Hg, asiopposed to a P 0 of approximately 1 04 Hg in the alveoli, a steep oxygen partial pressure gradient exists, and 0 2 diffuses

mm mm

rapidly

from the

,

alveoli into the

pulmonary

—

capillary

blood (Figure 22.17). Equilibrium that is, a Pq 7 of 104 Hg on both sides of the respiratory membrane usually occurs in 0.25 second, which is about one-third the time a red blood cell is in a pulmonary capillary (Figure 22.18). The lesson here is that the blood can flow through the pulmonary capillaries three times as quickly and still be adequately oxygenated. Carbon dioxide moves in the opposite direction along a much gentler partial pressure graHg) dient of about 5 Hg (45 Hg to 40 Hg. Carbon dioxuntil equilibrium occurs at 40 ide is then expelled gradually from the alveoli during expiration. Even though the 0 2 pressure gradient for

mm

—

mm

mm mm

mm

Chapter 22

Suppose

9

patient

a

is

receiving oxygen by mask.

condition of the arterioles leading into

What

is

What

is

The Respiratory System

855

the

0 2 -enriched alveoli?

the advantage of this response?

o2

V

co 2 in

Reduced

alveoli

Pulmonary

alveolar ventilation;

Reduced

arterioles

serving these alveoli

excessive perfusion

alveolar ventilation;

reduced perfusion

constrict

in alveoli

Enhanced

Pulmonary

alveolar ventilation;

Enhanced alveolar ventilation; enhanced perfusion

arterioles

serving these alveoli

inadequate perfusion

dilate

FIGURE 22.19 result in local

Ventilation-perfusion coupling. Autoregulatory events that matching of blood flow (perfusion) through the pulmonary capillaries

and conditions of alveolar

oxygen diffusion

ventilation.

much

is

steeper than the

C0 2

gra-

amounts of these gases are exchanged because C0 2 is 20 times more soluble in plasma and dient, equal

alveolar fluid than

02

.

Ventilation-Perfusion Coupling

must be a close match, or coupling, between ventilation (the amount of gas reaching the alveoli) and perfusion (the blood flow in pulmonary capillaries). As explained in Chapter 19 and illustrated in Figure 22.19, local autoregulatory mechanisms continuously respond to For gas exchange to be efficient, there

alveolar conditions.

In alveoli where ventilation low.

As

is

inadequate, P Ql

a result, the terminal arterioles constrict,

is

and

blood is redirected to respiratory areas where P 0 is high and oxygen pickup may be more efficient. In ,,

|

p

BuiLjoieiu SMOjje

'UdBAxo

asuodsaj

p

/(}///qe//e/\e

siu_[

oi /woy

poo/q

paiejip aq p/no/w

/Cauj_

alveoli

where ventilation

is

maximal, pulmonary

ar-

blood flow into the associated pulmonary capillaries. Notice that the autoregulatory mechanism controlling pulmonary vascular muscle is the opposite of the mechanism controlling most arterioles in the systemic circulation. While changes in alveolar P Qi affect the diameter of pulmonary blood vessels (arterioles), changes in alveolar P co cause changes in the diameters of the bronchioles. Passageways servicing areas where alveolar C0 2 levels are high dilate, allowing C0 2 to be eliminated from the body more rapidly, while those serving areas where Pco 2 1S low constrict. As a result of modifications made by these two syctems, alveolar ventilation and pulmonary perfusion are synchronized. Poor alveolar ventilation results in low oxygen and high carbon dioxide levels in the alveoli; consequently, the pulmonary arterioles constrict and the airways dilate, bringing air flow and blood flow into closer physiological match. High Po 2 and low Pco 2 i n tne alveoli cause respiratory passageways serving the alveoli to constrict, and terioles dilate, increasing

,

856

Unit IV

Maintenance of the Body

promote flushing of blood into the pulmonary capillaries. Although these homeostatic mechanisms

exchanges between the systemic capillaries and the

provide appropriate conditions for efficient gas exchange, they never completely balance ventilation and perfusion in every alveolus because of (1) the shunting of blood from the bronchial and coronary veins, (2) the effects of gravity, and (3) the occasional alveolar duct plugged with mucus. Consequently, blood in the pulmonary veins actually has a

the lungs (Figure 22.17). Tissue cells continuously

slightly lower

(104

mm

P Ql (100

mm

Hg) than alveolar

air

Hg) rather than the equality indicated in

Thickness and Surface Area of the Respiratory Membrane In healthy lungs, the respiratory membrane is only 0.5 to 1 (Jim thick, and gas exchange is usually very efficient.

If

become waterlogged and edematous

in pneumonia), the exchange dramatically.

for their

.

,

mm

mm

Under such

membrane

mm

Transport of Respiratory

HOMEOSTATIC IMBALANCE

the lungs

02

metabolic activities and produce C0 2 Because P Q in the tissues is always lower than that in the systemic arterial blood (40 Hg versus 104 Hg), 0 2 moves rapidly from the blood into the tissues until equilibrium is reached, and CO? moves quickly along its pressure gradient into the blood. As a result, venous blood draining the tissue capillary beds and returning to the heart has a P Ql of 40 Hg and a Pco, of 45 Hg. In summary, the gas exchanges that occur between the blood and the alveoli and between the blood and the tissue cells take place by simple diffusion driven by the partial pressure gradients of 0 2 and C0 2 that exist on the opposite sides of the exchange membranes.

use

mm

Figure 22.17.

••^J)^

tissue cells are essentially identical to those acting in

(as

thickens

conditions, even the total

time (0.75 s) that red blood cells are in transit through the pulmonary capillaries may not be enough for adequate gas exchange, and body tissues begin to suffer from oxygen deprivation. •

Gases by Blood Oxygen Transport External and internal respiration have been considered consecutively to emphasize their similarities, but keep in mind that it is the blood that transports 0 2 and 2 between these two exchange

C0

sites.

The greater the surface area of the respiratory membrane, the more gas can diffuse across it in a given time period. The alveolar surface area is enor-

mous

in healthy lungs. Spread flat, the total gas exchange surface of these tiny sacs in an adult 2 approximately 40 times male's lungs is about 60 greater than the surface area of his skin!

m

,

^iQ^ HOMEOSTATIC IMBALANCE In certain

pulmonary

diseases, the alveolar surface

area actually functioning in gas exchange

is

drasti-

This occurs in emphysema, when the walls of adjacent alveoli break through and the alveolar chambers become larger. It also occurs when tumors, mucus, or inflammatory material blocks gas

Molecular oxygen is carried in blood in two ways, bound to hemoglobin within red blood cells and dissolved in plasma (see Figure 22.22, p. 860). Oxygen is poorly soluble in water, so only about 1.5% of the oxygen transported is carried in the dissolved form. Indeed, if this were the only means of oxygen transport, a P Q of 3 atm or a cardiac output of 1 5 times normal would be required to provide the oxygen levels needed by body tissues! This problem, of course, has been solved by hemoglobin, and 98.5% of the oxygen ferried from the lungs to the tissues is carried in a loose chemical combination with hemoglobin. ,

cally reduced.

flow into the alveoli.

•

Internal Respiration: Capillary

Gas Exchange

in

the Body Tissues

In internal respiration, the partial pressure and diffusion gradients are reversed from the situation

pulmonary gas promoting gas

described for external respiration and

exchange.

However,

the

factors

Association of

Oxygen and Hemoglobin

As described in Chapter 17, hemoglobin (Hb) composed of four polypeptide chains, each bound

is

to

an iron-containing heme group (see Figure 17.4). Because the iron atoms bind oxygen, each hemoglobin molecule can combine with four molecules of 0 2 ,

and oxygen loading is rapid and reversible. The hemoglobin- oxygen combination, called oxyhemoglobin (ok"si-he"mo-glo'bin), is written Hb0 2 Hemoglobin that has released oxygen is called reduced hemoglobin, or deoxyhemoglobin, and is written HHb. Loading and unloading of 0 2 .

The Respiratory System

Chapter 22

857

can be indicated by a single reversible equation: Lungs

HHb

+

02

Hb0 2

t

+

H+

Tissues first C* 2 molecule binds to iron, the Hb shape. As a result, it more readily changes molecule takes up two more 0 2 molecules, and uptake of the fourth is even more facilitated. When all four heme groups are bound to 0 2/ a hemoglobin molecule is said to be fully saturated. When one, two, or three oxygen molecules are bound, hemoglobin is partially saturated. By the same token, unloading of one oxygen molecule enhances the unloading of the next, and so on. Thus, the affinity of hemoglobin for oxygen changes with the extent of oxygen saturation, and both loading and unloading of oxygen are very

After the

efficient.

which Hb reversibly binds or releases 0 2 is regulated by Po 2 temperature, blood pH, P C cv and blood concentration of an organic chemical called BPG. These factors interact to ensure ade-

The

rate at

,

quate deliveries of

relationship between the degree of hemoglobin saturation

and the P Ql

of blood

is

not

of Figure

mm

mm

,

.

venous blood.

The nearly complete saturation of Hb in arterial blood explains why breathing deeply (which increases both the alveolar and arterial blood P Qi above 104 Hg) causes very little increase in the D 2 saturation of hemoglobin. Remember, P Ql measurements indicate only the amount of 0 2 dissolved in plasma, not the amount bound to hemoglobin. However, P 0 values are a good index of lung function, and when arterial P 0l is significantly less than

mm

,

alveolar

P Ql/ some degree

of respiratory

impairment

exists.

A

hemoglobin saturation curve (Figure 22.20) reveals two other important facts. First, Hb is almost completely saturated at a P Q of 70 Hg, and further increases in P Ql produce only small in,

creases in

0 2 binding. The

Po 2 (mm Hg)

FIGURE 22.20 Oxygen-hemoglobin dissociation curve. Changes in Hb saturation and blood 0 2 content as Po 2 changes. Notice that hemoglobin is almost completely saturated at a P

combines more readily with carbon dioxide than does oxygenated hemoglobin (see the discussion of the Haldane effect on p. 861).

4.

.

The Respiratory System

3.

As bicarbonate ion in plasma (about 70%).

Most carbon dioxide molecules entering the plasma quickly enter the RBCs, where most

of the reactions that prepare carbon dioxide for transport as bicarbonate ions (HC0 3 ~) in plasma occur. As

C0 2

when

illustrated in Figure 22.22a,

diffuses

into the RBCs, it combines with water, forming carbonic acid (H 2 C0 3 ). H 2 CO,3 is unstable and quickly dissociates into hydrogen ions and bicarbonate ions:

C0 2

+

Carbon

H20

— H C0 — H 2

Water

Carbonic

dioxide

+

3

Hydrogen ion

acid

+

HC0 3

Bicarbonate ion

Although this reaction also occurs in plasma, it is thousands of times faster in RBCs because they (and not plasma) contain carbonic anhydrase (karbon'ik an-hi'dras), an enzyme that reversibly catalyzes the conversion of carbon dioxide and water to carbonic acid. Hydrogen ions released during the reaction bind to Hb, triggering the Bohr effect; thus, 0 2 release is enhanced by C0 2 loading (as HC0 3 ~). Because of the buffering effect of Hb, the + liberated H causes little change in pH under resting conditions. Hence, blood becomes only slightly more acidic (the pH declines from 7.4 to 7.34) as it passes through the tissues. Once generated, HC0 3 ~ diffuses quickly from the RBCs into the plasma, where it is carried to the lungs. To counterbalance the rapid outrush of these anions from the RBCs, chloride ions (Cl~) move from the plasma into the RBCs. This ion exchange process is called the chloride shift. In the lungs, the process

is

reversed (Figure

As blood moves through the pulmonary capillaries, its Pco declines from 45 mm Hg to 40 mm Hg. For this to occur, C0 2 must first be freed 22.22b).

9

from

HC0

~ reenters the "bicarbonate housing." 3 (and moves into the plasma) and binds + to form carbonic acid, which is then split

its

RBCs

CP

with H by carbonic anhydrase to release C0 2 and water. This C0 2 along with that released from hemoglobin and from solution in plasma, then diffuses along ,

860

Unit IV

Maintenance of the Body

diagram (a), as 0 2 is being unloaded from hemoglobin, the hemoglobin also sheds some nitric oxide. What possible role does the NO play in this gas exchange process? In

Interstitial fluid

C0 2 C0 2

C0 2 (dissolved

'

Slow

C0 2 + H 2 0

'

Binds to

plasma)

in

»

plasma proteins

H 2 C0 3

HCO3-

+

H+

**HCO, - Chloride

HC0 3~ + H

H 2 C0 3

C0 2 + H 2 0

cr

+

shift

Carbonic

anhydrase

C0 2 + Hb = HbC02

C\ ~


is

40

mm

Hg and is maintained within ±3 mm Hg of this level Key: stimulus

I

I

Initial

I

I

Physiological response

Result

FIGURE 22.26 Negative feedback mechanism by which in Pco anc blood pH regulate ventilation. 2

changes

*

by an exquisitely sensitive homeostatic mechanism that is mediated mainly by the effect that rising C0 2 levels have on the central chemoreceptors of the brain stem (Figure 22.26). C0 2 diffuses easily from the blood into the cerebrospinal fluid, where it is hydrated and forms carbonic acid. As the acid dissoci+ ates, H is liberated. This is the same reaction that occurs when C0 2 enters RBCs (see p. 859). Unlike

RBCs or plasma, however, cerebrospinal fluid contains virtually no proteins that can buffer the + added Thus, as Pcot levels rise, a condition referred to as hypercapnia (hi"per-kap'ne-ah), the cerebrospinal fluid pH drops, exciting the central chemoreceptors, which make abundant synapses with the respiratory regulatory centers. As a result, the depth and perhaps the rate of breathing are increased. This breathing pattern, called hyperventilation, enhances alveolar ventilation and quickly flushes C0 2 out of the blood, increasing blood pH. An elevation of only 5 Hg in arterial P C o 9 results in a doubling of alveolar ventilation, even

H

Influence of Higher Brain Centers

Hypothalamic Controls Acting through the limbic system, strong emotions and pain activate sympathetic centers in the hypothalamus that can modify respiratory rate and depth by sending signals to the respiratory centers. For example, have you ever touched something cold and clammy and gasped? That response was mediated through the hypothalamus. So too is the breath holding that occurs when we are angry and the increased respiratory rate that occurs when we are excited. A rise in body temperature acts to increase the respiratory rate, while a drop in body temperature produces the opposite effect; and sudden chilling of the body (a dip in the north Atlantic Ocean in late October) can cause cessation of breathing (apnea)

— or

at the very least, gasping.

.

mm

when

arterial

When Po

9

to elevated

normally

02

and pH are unchanged. are below normal, the response

levels

and pH P CO is even -,

self-limiting,

greater.

Hyperventilation

ending

when homeostatic

blood P co levels are restored. ,

is

Chapter 22

C0 2 levels act as H levels that prod

Notice that while rising initial

stimulus,

rising

it is

The Respiratory System

865

the

4

the

central chemoreceptors into activity. In the final analysis, control of breathing during rest is aimed

primarily at regulating the

H+

concentration in the

Brain

brain.

HOMEOSTATIC IMBALANCE Sensory nerve

A person

experiencing an anxiety attack may hyperventilate involuntarily to the point where he or she becomes dizzy or faints. This happens because low C0 2 levels in the blood (hypocapnia) cause cerebral blood vessels to constrict, reducing brain perfusion

in

branch

of

glossopharyngeal)

External carotid artery

-

and producing cerebral ischemia. Such attacks may be averted by breathing into a paper bag because then the air being inspired is expired air, rich in carbon dioxide, which causes carbon dioxide to be re-

Internal carotid artery

Carotid body

Common

•

tained in the blood.

fiber

cranial nerve IX (pharyngeal

carotid artery

X

Cranial nerve

(vagus nerve)

When

P COl is abnormally low, respiration is inand becomes slow and shallow; that is, hypoventilation occurs. In fact, periods of apnea hibited

may

(breathing cessation)

Sensory nerve

occur until arterial Pco 2

and again stimulates respiration. Sometimes swimmers voluntarily hyperventilate so that they can hold their breath longer during

fiber in

cranial nerve

X

Aortic bodies

in

rises

swim meets. This

is

Aorta

incredibly dangerous for the

following reasons. Blood

much below 60%

aortic arch

02

content rarely drops

normal during regular breathholding, because as P 0l drops, P co rises enough to make breathing unavoidable. However, strenuous hyperventilation can lower P co so much that a lag period occurs before it rebounds enough to stimulate respiration again. This lag may allow oxygen levels to fall well below 50 Hg, causing the swimmer of

Heart

,

,

mm

to black out (and perhaps drown) before he or she has the urge to breathe.

Influence of P Cells sensitive to arterial 0 2 0z levels are found in the peripheral chemoreceptors, that is, in the aortic bodies of the aortic arch and in the carotid bodies at the bifurcation of the common carotid arteries (Figure 22.27).

Those

FIGURE 22.27

Location of the peripheral

chemoreceptors in the carotid and aortic bodies. Also shown are the sensory pathways from these receptors through cranial nerves IX and X to the respiratory center in the medulla.

in the carotid

main oxygen sensors. Under normal conditions, the effect of declining Po 2 on ventilation is slight and mostly limited to en-

bodies are the

Hg. As central chemoreceptors then begin to suffer

hancing the sensitivity of central receptors to increased Pco,- Arterial P Q , must drop substantially, to at least 60 Hg, before 0 2 levels become a major stimulus for increased ventilation. This is not as strange as it may appear. Remember, there is a huge reservoir of 0 2 bound to Hb, and Hb remains almost entirely saturated unless or until the P Q of alveolar gas and arterial blood falls below 60

from 0 2 starvation, the oxygen-poor blood produces NO-derived compounds called 5-nitrosothiols, or SNOs, which act on the respiratory center to induce rapid breathing. At the same time, the peripheral chemoreceptors become excited and stimulate the respiratory centers to increase ventilation, even if P C o 2 is normal. Thus, the peripheral chemoreceptor system can maintain ventilation when alveolar 0 2 levels are low even though brain stem centers are depressed by hypoxia.

mm

,

mm

866

Maintenance of the Body

Unit IV

LOOK

Dangerous Raptures of the Deep

the nonswimmers among us Even are beckoned by photos of scuba

than-normal pressure. Thus descent not usually a problem, unless divers

nitrogen gas appears to "boil" from the

is

think enviously. But hidden beneath

descend below 100 feet and remain there for an extended time. Although nitrogen ordinarily has little effect on body functioning, hyperbaric conditions for an extended time

that veneer of breathtaking beauty

force so

divers examining brightly

colored coral and other ocean creatures as they glide effortlessly through

"What

sparkling blue water.

life-threatening

a life,"

we is

danger for the inexpeand the unlucky.

rienced, the careless, In

addition to the significant

risk

the blood that

nitrogen into solution

is

far

more soluble

drowning, scuba divers are exposed to

water, so

the omnipresent danger of two other

lipid-rich tissues

medical emergencies

—

air

embolism

provokes

it

in

it

lipids

in

than

tends to concentrate

in

such as the central

become

cles can

cause excruciating muscu-

loskeletal pain,

commonly

called the

"bends." Other signs of this decom-

mood

changes,

numbness, "migrating" skin rashes, and a syndrome called chokes. Chokes, or cardiovascular bends, involves substernal pain, cough-

seizures, nausea,

in

nervous system, bone marrow, and

fluids.

pression sickness are

a narcotic

effect called nitrogen narcosis. Nitro-

gen

of

much

and out of solution in the body Gas bubbles in blood represent potentially lethal emboli, and those formed within joints, bones, and mustissues

ing, dyspnea, and, in severe cases, shock due to gas bubbles in the pul-

fat

and decompression sickness. As divers descend to greater and

deposits. Divers

greater depths underwater, the pres-

why

and appear to be intoxicated, which is this condition is sometimes called

signs usually appear within an hour of

sure on their bodies rises proportion[1 atmosphere (760 mm Hg) of pressure for each 0 m (33 ft) of descent] because of the increasing weight of the water. Scuba gear (selfcontained underwater breathing appa-

ately

1

ratus)

has freed divers from

lines to

air

the surface and heavy pressur-

ized suits

because

equalization of the

it

permits continual

air

pressure (pro-

vided by the mixture of compressed in the tank) with the water pressure; that

is,

air

air

enters the lungs at a higher-

dizzy, giddy,

surfacing, they can

be delayed

as 36 hours. Even

divers experienced

compression sickness can also strike at high altitudes, such as in unpressurized aircraft flying above 18,000 feet.) Assuming divers take care to avoid these narcotizing effects, and ascend to

no apparent problems underwater, they

This situation usually occurs

the surface gradually (see the graph),

panic after aspirating seawater or en-

dissolved nitrogen gas can be driven

countering other hazards, such as

out of the tissues and eliminated by the

equipment

lungs without problems. But

rough waters. Under such conditions,

cent

is

rapid, the P N2

if

disease

(e.g.,

C0 2

P co is chronically elevated and, as a result, chemoreceptors become unresponsive to this chemical stimulus. In such cases, a declining Pq 2 acting on the oxygen-sensitive peripheral chemorearterial

,

ceptors provides the principal respiratory stimulus,

the hypoxic drive. Thus, gas mixtures administered to such patients during respiratory distress are only slightly enriched with 0 2 because inspiration of

pure oxygen would stop their breathing by removing their respiratory stimulus (low Po levels). • 2

Changes in arterial Influence of Arterial pH can modify respiratory rate and rhythm even when CO 2 and 0 2 levels are normal. Because little

pH

the as-

decreases

H+

diffuses

on

if

could experience symptoms

as long

later.

Gas emboli may also result if divers ascend suddenly and without exhaling.

failure,

the alveoli are

when they

strong currents, or

likely to rupture.

If

connections occur between the alveoli

abruptly and the poorly soluble

because of pulmonary emphysema and chronic bronchitis), retain

Although these

"rapture of the deep." (Despite this

fluid,

who

capillaries.

nickname, nitrogen narcosis and de-

HOMEOSTATIC IMBALANCE In people

monary

from the blood ;nto the cerebrospinal

the direct effect of arterial

H

concentration

compared generated by elevations in Pco 2

central chemoreceptors +

to the effect of

H+

is

insignificant

-

The

increased ventilation that occurs in response to falling arterial pH is mediated through the periph-

chemoreceptors. + concentration Although changes in P C q 2 and are interrelated, they are distinct stimuli. A drop in blood pH may reflect C0 2 retention, but it may also result from metabolic causes, such as accumulation of lactic acid during exercise or of fatty (or other organic) acids in patients with poorly controlled diabetes mellitus. Regardless of cause, as arterial pH declines, respiratory system controls attempt to compensate and raise the pH by eliminating C0 2 (and carbonic acid) from the blood; thus, respiratory rate and depth increase. eral

H

Chapter 22

The Respiratory System

867

Approximate water depth in meters (feet)

9

m

(30

No decompression needed

ft.)

18m (60

27 (90

40

ft.)

m ft.)

/ /

m

(130

Decompressio n needed

ft.)

2

1

Duration

in

hours

Even with modern scuba gear, divers need to know how to adjust from high underwater pressures to the lower pressures at the surface.

and the pulmonary bloodstream,

life-

threatening gas emboli develop with the

first

breath of

air at

the surface, and

the related problems develop within

two minutes. Since divers typically ascend head-up, the emboli usually invade the cerebral circulation. Seizures, localized motor and sensory deficits, and unconsciousness are all possibilities.

Indeed,

many

scuba-related drown-

appear to follow loss of consciousarterial gas embolism. The usual and most effective treatment for decompression sickness is

.

Rising

C0 2

C0 2

therapy

need

for treat-

.

.

.

slowly.

When

Under normal

a

gas embolus

medications are given

until

is

effects;

C0 2

know

risks

high P 0 levels diminish the effective,

stimulation.

3. When arterial P Q falls below 60 mm Hg, it becomes the major stimulus for respiration, and ,

ventilation is increased via reflexes initiated by the peripheral chemoreceptors. This may increase 0 2 loading into the blood, but it also causes hypocapnia (low Pco 2 blood levels) and an increase in blood pH, both of which inhibit respiration. 4.

Changes in

arterial

pH

resulting

from

C0 2 reten-

tion or metabolic factors act indirectly through the peripheral chemoreceptors to promote changes in

which in turn modify arterial P C o 2 and pH. Arterial pH does not influence the central chemoreceptors directly.

ventilation,

blood P Ql affects breathing only indirectly by influencing chemoreceptor sensitivity to changes in P C o Low P Ql augments r conditions,

sure that divers

and are well trained in using their equipment. Assuming that is done, the vacation should be GREAT!

hyperbaric

ness of

to avoid the

the potential

therapy can begin.

PC o 2

is

ment by making

is

suspected, oxygen and antiseizure

respiration. 2.

alcohol or exercising strenuously before

pression and then redoing decompression

levels are the

As

to

The best

here:

tory stimulant.

content or

a dive also increase the risk.

most powerful respirahydrated in cerebrospinal + fluid, liberated H acts directly on the central chemoreceptors, causing a reflexive increase in breathing rate and depth. Low Pco levels depress 2 1

fat

more vulnerable decompression sickness. Consuming

recent limb injuries are

hyperbaric therapy: reinstituting com-

Summary of Interactions of P C o 2 i PO z , and Arterial pH Although every cell in the body must have 0 2 to live, the body's need to rid itself of C0 2 is the most important stimulus for breathing in a healthy person. However, C0 2 does not act in isolation, and various chemical factors enforce or inhibit one another's effects. These interactions are summarized

People with high body

ings

ness due to

868

Unit IV

Maintenance of the Body

and pulmonary perfusion

Respiratory Adjustments

are as well

exercise as during rest. Rather,

Adjustments During Exercise Respiratory adjustments during exercise are geared both to intensity and duration of the exercise. Working muscles consume tremendous amounts of 0 2 and produce large amounts of C0 2 thus, ventilation can increase 10 to 20 fold during vigorous exercise. Breathing becomes deeper and more vigorous, but the respiratory rate may not change significantly. This breathing pattern is called hyperpnea (hi"perpne'ah) to distinguish it from the deep and often rapid ;

pattern of hyperventilation. Also, the respiratory changes seen in hyperpnea match metabolic de-

mands and blood

02

so do not lead to significant changes in

and

C0 2

levels.

By

contrast, hyperventila-

may

provoke excessive ventilation, resulting in low Pco, an d alkalosis. Exercise-enhanced ventilation does not appear to be prompted by rising P C o 2 an d declining Pq 2 and pH in the blood for two reasons. First, ventilation increases abruptly as exercise begins, followed by a gradual increase, and then a steady state of ventilation. When exercise stops, there is an initial small but abrupt decline in ventilation rate, followed by a gradual decrease to the pre-exercise value. Second, although venous levels change, arterial P C o 2 and Po 2 levels remain surprisingly constant during exercise. In fact, P C o 2 maY decline to below normal and Pq 2 may rise slightly because of the efficiency of the respiratory adjustments. Our present understanding of the mechanisms that produce these observations is sketchy, but the most accepted explanation is as foltion

lows.

The abrupt

increase in ventilation that occurs as exercise begins reflects interaction of three neural factors: 1.

Psychic stimuli (our conscious anticipation of ex-

ercise)

tal

Simultaneous cortical motor activation of skelemuscles and respiratory centers

3.

Excitatory impulses reaching respiratory centers

2.

from proprioceptors in moving muscles, tendons, and joints.

The subsequent

gradual increase and then plateau-

ing of respiration probably reflect the rate of livery to the lungs (the

"C0 2

The small but abrupt

C0 2 de-

flow").

decrease in ventilation that occurs as exercise ends reflects the shutting off of the neural control mechanisms. The subsequent gradual decline to baseline ventilation likely reflects a decline in the 2 flow that occurs as the oxygen debt is being repaid. The rise in lactic acid levels that contributes to 0 2 debt is not a result of inadequate respiratory function, because alveolar ventilation

C0

it

matched during

reflects cardiac out-

put limitations or inability of the skeletal muscles to further increase their oxygen consumption. In light of this fact, the practice of inhaling pure 0 2 by mask, used by some football players to replenish their "oxygen-starved" bodies as quickly as possible, is useless. The panting athlete does have an 0 2 deficit, but inspiring extra oxygen will not help, because the short-

age

is

in the muscles

— not the lungs.

Adjustments

at

Most Americans

live

High Altitude

between sea level and an altitude of approximately 8000 feet. In this range, differences in atmospheric pressure are not great enough to cause healthy people any problems when they spend brief periods in the higher-altitude areas. However, when you travel quickly from sea level to elevations above 8000 ft, where air density and Pq 2 are lower, your body responds with symptoms of acute mountain sickness (AMS) headaches, shortness of breath, nausea, and dizziness. AMS is common in travelers to ski resorts such as Vail, Colorado (8120 ft), and Brian Head, Utah (a heart-pounding 9600 ft). In severe cases of AMS, lethal pulmonary and cerebral edema may occur. When you move on a long-term basis from sea level to the mountains, your body begins to make respiratory and hematopoietic adjustments via an adap-

—

response called acclimatization. As already P Q , cause the central chemoreceptors to become more responsive to intive

explained, decreases in arterial creases in

Pcov and

a substantial decline in Pqt directly stimulates the peripheral chemoreceptors. As a result, ventilation increases as the brain attempts to restore gas exchange to previous levels. Within a few days, the minute respiratory volume stabilizes at a level 2-3 L/min higher than the sea level rate. Be-

cause increased ventilation arso reduces arterial C0 2 levels, the Pcot of individuals living at high altitudes is typically below 40 Hg (its value at sea level). Because less 0 2 is available to be loaded, highaltitude conditions always result in lower-thannormal hemoglobin saturation levels. For example, at about 19,000 ft above sea level, 0 2 saturation of arterial blood is only 67% (compared to nearly 98% at sea level). But Hb unloads only 20-25% of its oxygen at sea level, which means that even at the reduced saturations at high altitudes, the 0 2 needs of the tissues are still met adequately under resting conditions. Additionally, at high altitudes Hb releases more to the capillary blood in the tissues and hemoglobin's affinity for 0 2 is reduced because of increases in BPG concentration, with the result that more 0 2 is released to the tissues during each circulatory round.

mm

NO

Chapter 22

Although the tissues in a person at high altitude oxygen under normal conditions, problems arise when all-out efforts are demanded of the cardiovascular and respiratory systems (as discovered by U.S. athletes competing in the 1968 summer Olympics on the high mesa of Mexico City, at 7370 ft). Unless one is fully acclimatized, such conditions almost guarantee that body tissues will severely hypoxic.

When blood 0 2

levels decline, the kidneys accel-

erate production of erythropoietin,

which stimulates

bone marrow production of RBCs (see Chapter 17). This phase of acclimatization, which occurs slowly, provides long-term compensation for living at high

869

Tobacco smoke

receive adequate

become

The Respiratory System

•

Air pollution

a-1 antitrypsin

deficiency

3? rBreakdown

Continual bronchial irritation and inflammation

of elastin in

connective tissue

of

Chronic bronchitis Bronchial edema,

Emphysema

chronic productive cough,

walls, lung fibrosis,

bronchospasm

air

lungs

Destruction of alveolar trapping

Airway obstruction or air trapping

altitudes.

Dyspnea Frequent infections

Homeostatic Imbalances of the Respiratory System The

respiratory system

is

Abnormal

particularly vulnerable to

wide open to airborne pathogens. Many of these inflammatory conditions, such as rhinitis and laryngitis, were considered earlier in the chapter. Here we turn our attention to the infectious diseases because

most disabling

monary

ventilation-

perfusion ratio

Hypoxemia

it is

Hypoventilation

FIGURE 22.28

The pathogenesis of COPD.

disorders: chronic obstructive pul-

and and lung cancer are living proof of the devastating effects of cigarette smoking on the body. Long known to promote cardiovascular disease, cigarettes are perhaps even more effective at destroydisease (COPD), asthma, tuberculosis,

lung cancer.

COPD

inflammation leads to lung

and invariably the lungs lose their elasticity. Arterial 0 2 and C0 2 levels remain essentially normal until late in the disease.

ing the lungs.

As

the lungs

become

collapse during expiration

fibrosis,

less elastic, the

air. This has two important consequences: Ac1 cessory muscles must be enlisted to breathe, and victims are perpetually exhausted because breathing requires 15-20% of their total body energy supply (as opposed to 5% in healthy individuals). (2) For

of

Chronic Obstructive Pulmonary Disease The chronic

obstructive pulmonary diseases (COPD), exemplified best by chronic bronchitis and obstructive emphysema, are a major cause of death and disability in the United States and are becoming increasingly prevalent. These diseases have certain features in 1.

common

Patients

(Figure 22.28):

almost invariably have a history of

smoking. 2.

Dyspnea

ing often referred to as "air hunger," occurs

progressively 3.

(

complex reasons, the bronchioles open during

more

Coughing and frequent pulmonary

common. 4. Most COPD

and

gets

severe.

infections are

victims develop respiratory failure

(accompanied by hypoxemia,

C0 2

retention,

and

respiratory acidosis).

Obstructive emphysema is distinguished by permanent enlargement of the alveoli, accompanied by deterioration of the alveolar walls. Chronic

)

inspi-

ration but collapse during expiration, trapping huge

volumes

This hyperinflation leads to development of a permanently expanded "barrel chest" and flattens the diaphragm, thus reducing ventilation efficiency. of air in the alveoli.

Damage

(disp-ne'ah), difficult or labored breath-

airways

and obstruct the outflow

pulmonary capillaries increases resistance in the pulmonary circuit, forcing the right ventricle to overwork and consequently become enlarged. Emphysema victims are sometimes called to the

"pink puffers" because their breathing is labored, but they do not become cyanotic (blue) because gas exchange remains surprisingly adequate until late in the disease. In addition to cigarette smoking, hereditary factors

may help

(e.g.,

alpha- 1 antitrypsin deficiency)

to cause emphysema in some patients. In chronic bronchitis, inhaled irritants lead to chronic excessive mucus production by the mucosa of the lower respiratory passageways and to

870

Unit IV

Maintenance of the Body

inflammation and fibrosis of that mucosa. These responses obstruct the airways and severely impair lung ventilation and gas exchange. Pulmonary infections are frequent because bacteria thrive in the stagnant pools of mucus. Patients are sometimes called "blue bloaters" because hypoxia and C0 2 retention occur early in the disease and cyanosis is common. However, the degree of dyspnea is usually moderate

compared

to that of

emphysema

sufferers.

ment

may

contribute to the develop-

of chronic bronchitis.

COPD is routinely treated with bronchodilators and corticosteroids in aerosol form inhalers Severe dyspnea and hypoxia mandate oxygen use. A highly }.

|

controversial surgical treatment introduced in 1994,

lung volume reduction surgery-, has been performed on some emphysema patients. Part of the grossly enlarged lungs is removed to give the remaincalled

ing lung tissue

room

to expand.

At

least in the short

term, enough breathing capacity is restored to allow those patients to live something close to a normal life.

(The average increase in lung function

is

55%.)

Asthma Asthma

is characterized by episodes of coughing, dyspnea, wheezing, and chest tightness alone or in combination. Most acute attacks are accompanied by a sense of panic. Although sometimes classed with COPD because it is an obstructive disorder, asthma is marked by acute exacerbations followed by

—

symptom-free periods.

The cause of asthma has been hard to pin down. Initially it was viewed as a consequence of bronchospasm air,

by various factors such as cold or allergens. However, when it was dis-

triggered

exercise,

number

of

asthma deaths doubled. Sadly, and mortality has come

—

about despite changes in drug therapy a change in focus from inhaled bronchodilators, which bring relief in minutes, to inhaled steroids, which act more slowly but reduce the inflammatory response and the frequency of episodes that came from a greater understanding of the disease.

—

In addi-

tion to the major factor of cigarette smoking, envi-

ronmental pollution

1989, the

this increase in morbidity

Tuberculosis Tuberculosis (TB), the infectious disease caused by the bacterium Mycobacterium tuberculosis, is spread by coughing and primarily enters the body in inhaled air. TB mostly affects the lungs but can spread through the lymphatics to affect other organs. One-third of the world's population is infected, but most people never develop active TB because a massive inflammatory and immune response usually contains the primary infection in fibrous, or calcified, nodules (tubercles) in the lungs. However, the bacteria survive in the nodules and when the person's immunity is low, they may break out and cause symptomatic TB, involving fever, night sweats, weight loss, a racking cough, and spitting up blood. Until the 1930s, TB was responsible for onethird of all deaths among 20- to 45-year-old U.S. adults. With the advent of antibiotics in the 1940s, this killer was put into retreat and its prevalence declined dramatically. However, since 1985 there has been an alarming increase in TB, and it has become a leading cause of death from infectious disease. Most of this increase is associated with HIV-infected individuals, especially those who abuse intravenous drugs and reside in shelters for the homeless. The TB bacterium grows very slowly and drug therapy entails a 12-month course of antibiotics. Most indi-

HIV and TB

on

covered that bronchoconstriction has relatively little effect on air flow through the lungs, researchers probed more deeply and found that in asthma, active inflammation of the airways comes first. The airway inflammation is an immune response under the control of T H 2 cells, a subset of T lymphocytes that, by secreting certain interleukins, stimulate the production of IgE and recruit inflammatory cells (notably eosinophils! to the site. Once someone has allergic asthma, the inflammation persists even during symptom-free periods and makes the airways hypersensitive to almost any irritant. (It now appears the most common triggers are in the home the allergens from dust mites, cockroaches, cats, dogs, and fungi. Once the airway walls are thickened with inflammatory exudate, the effect of bronchospasm is vastly magnified and can dramatically reduce

viduals infected with

air flow.

deaths in the United States.

Since the 1980s the number of asthma cases has been increasing, and in the decade from 1979 to

smoking (more than 90% of lung cancer patients were smokers), is increasing

—

I

test negative

TB screening tests because of their weakened immune system. (The TB test depends on detecting anti-TB antibodies in the patient.) Then when they for TB, many fail to complete the drug course and pass on their microbes to others. Even more alarming is that deadly drug-resistant TB strains are emerging in patients who stop taking the drugs (about 20% of the total treated). The threat of TB epidemics is so real that health centers in some cities are detaining such patients in sanitariums against their will for as long as it takes to complete a

become symptomatic

cure.

Lung Cancer Lung cancer accounts

for fully one-third of cancer

associated with cigarette

Its

incidence, strongly

Chapter 22

(b) 5

FIGURE 22.29 (a)

The Respiratory System

871

weeks

Embryonic development of the respiratory system.

Anterior superficial view of the embryo's head, (b) Left lateral view of the

developing lower respiratory passageway mucosae.

daily.

In both sexes, lung cancer

is

lent type of malignancy. Its cure rate

Most victims

most preva-

the is

notoriously

one year of diagnosis; overall five-year survival of those with lung cancer is about 7%. Because lung cancer is aggressive and metastasizes rapidly and widely most cases are not low.

die within

diagnosed until they are well advanced. Lung cancer appears to follow closely the oncogene-activating steps outlined in A Closer Look in Chapter 4. Ordinarily nasal hairs, sticky mucus, and cilia do a fine job of protecting the lungs from chemical and biological irritants, but when one smokes, these devices are overwhelmed and eventually stop functioning.

Continuous

irritation

prompts

more mucus, but smoking

the production of

para-

mucus. Mucus pooling pulmonary infections, including

lyzes the cilia that clear this

leads to frequent

pneumonia, and

COPD.

However,

it is

effects of the "cocktail" of free radicals

the irritant

and carcino-

gens in tobacco smoke that eventually translate into lung cancer. The three most common types of lung cancer are (1)

squamous

which

cell

carcinoma (20-40%

nomas cause problems beyond their effects on the lungs because they become ectopic sites of hormone production. For example, some secrete ACTH (leading to Cushing's disease) or calcitonin (which results in hypocalcemia).

Complete removal

of the diseased lung has the

and providing a open to few lung cancer

greatest potential for prolonging cure.

However, this choice

is

life

patients because the cancer has often metastasized before

it is

discovered. In

most

cases, radiation ther-

apy and chemotherapy are the only options, but only small cell carcinoma is responsive to chemotherapy. However, this picture may change soon. Most lung cancers other than small cell carcinoma result from absence or mutation of the tumor suppressor gene p53 or through action of the K-ras oncogene. By infusing tumor cells with retroviruses carrying working p53 genes or K-ras gene inhibitors, researchers have achieved an 80% cure rate in mice and are optimistic that similar results might be obtained in

humans.

of cases),

arises in the epithelium of the bronchi or their

and tends to form masses that cavitate (hollow out) and bleed, (2) adenocarcinoma (25-35%), which originates in peripheral lung areas as solitary nodules that develop from bronchial glands and alveolar cells, and (3) small cell carcinoma (20-25%), which contains lymphocyte-like cells that originate in the primary bronchi and grow larger subdivisions

aggressively in small grapelike clusters within the

mediastinum. Subsequent metastasis from the mediastinum is especially rapid. Some small cell carci-

Developmental Aspects of the Respiratory System Because embryos develop in a cephalocaudal (headto-tail) direction, the upper respiratory structures appear first. By the fourth week of development, two thickened plates of ectoderm, the olfactory placodes

on the anterior aspect of the head (Figure 22.29). These quickly invaginate to form olfactory pits that form the nasal cavities. The (plak'ods), are present

olfactory pits then extend posteriorly to connect

)

872

Unit IV

Maintenance of the Body

with the developing foregut, which forms same time from the endodermal germ layer.

at the

CP

The epithelium of the lower respiratory organs develops as an outpocketing of the foregut endoderm, which becomes the pharyngeal mucosa. This protrusion, called the laryngotracheal bud, is present by the fifth week of development. The proximal part of the bud forms the tracheal lining, and its distal end splits and forms the mucosae of the bronchi and all their subdivisions, including (eventually) the lung alveoli. By the eighth week, mesoderm covers these ectoderm- and endoderm-derived linings and forms the walls of the respiratory passageways and the stroma of the lungs. By 28 weeks, the respiratory system has developed sufficiently to allow a baby born prematurely to breathe on its own. As noted earlier, infants born before this time tend to exhibit infant respiratory distress

syndrome resulting from

inadequate surfactant production. During fetal life, the lungs are filled with fluid and all respiratory exchanges are made by the placenta. Vascular shunts cause circulating blood to largely bypass the lungs (see Chapter 28, p. 1 127). At birth, the fluid-filled pathway is drained, and the respiratory passageways fill with air. As the Pco 2 the baby's blood rises, the respiratory centers are excited, causing the baby to take its first breath. The alveoli inflate and begin to function in gas exchange, but it is nearly two weeks before the lungs are fully

m

inflated.

^(J)^

reaeh the membrane and perform its normal role. Consequently, less is secreted and less water follows, resulting in the thick mucus typical of CF. A new CF study that dovetails with earlier findings indicates that other forces in the lungs initiate the downward spiral typical of this disease. It appears that infection of CF victims' lungs with the bacterium Pseudomonas aeruginosa trips a genetic switch that causes the disabled cells to churn out oceans of abnormal mucin (the primary component of mucus). The bacteria then feed on the stagnant pools of mucus and keep sending signals to the cells to make more. Toxins released by the bacteria and the local inflammatory reaction set up by the immune response both damage the lungs. Unable to reach the bacteria embedded in the mucus, the immune cells begin to attack the lung tissue, turning the air sacs into bloated cysts. Three lines of CF research being pursued are 1 using disabled cold viruses to carry normal CFTR genes into respiratory tract mucosa cells, (2) prodding another channel protein to take over the duties of transporting Cl~, and (3) developing techniques to free the CFTR protein from the ER. Scientists have reversed the signs of CF in mice by feeding them decosahexaenoic acid (DHA), a fatty acid found in fish oils. DHA-based drug testing in humans began in (

2000 after it was demonstrated that CF patients also have significant fatty acid imbalances in organs affected by the disease. •

The

HOMEOSTATIC IMBALANCE

Important birth defects of the respiratory system include cleft palate (described in Chapter 7) and cystic fibrosis. Cystic fibrosis (CF), the most common lethal genetic disease in the U.S., strikes

respiratory rate

is

highest in newborn in-

fants (40-80 respirations per minute). At five years

one out

of

every 2400 U.S. births. CF causes oversecretion of a viscous mucus that clogs the respiratory passages, providing a breeding ground for airborne bacteria

it is around 25 per minute, and in adults it between 12 and 18 per minute. In old age, the rate often increases again. At birth, only about one-

of age is

number

sixth of the final

of alveoli are present.

The

that predisposes the child to fatal respiratory infec-

lungs continue to mature and more alveoli are formed until young adulthood. However, if smoking begins in the early teens, the lungs never completely mature, and those additional alveoli are lost

tions that can be treated only by a lung transplant.

forever.

The

In infants, the ribs take a nearly horizontal course. Thus, infants rely almost entirely on descent of the diaphragm to increase thoracic volume for inspiration. By the second year, the ribs are positioned

disease also impairs food digestion by clogging

ducts that deliver pancreatic enzymes and bile to the small intestine, and sweat glands of CF patients produce an extremely salty perspiration. Conventional therapy for CF has been mucusdissolving drugs, "clapping" the chest to loosen the

more

obliquely,

CFTR

an essential amino acid and so it gets "stuck" in the endoplasmic reticulum, unable to lacks

of breathing is es-

tablished.

thick mucus, and antibiotics to prevent infection. At the root of CF is a faulty gene that codes for

the CFTR (cystic fibrosis transmembrane conductance regulator) protein. The normal CFTR protein works as a membrane channel to control Cl~ flow in and out of cells. In those with the mutated gene,

and the adult form

HOMEOSTATIC IMBALANCE Most

respiratory system problems that occur are the

terial infections or

piece of food. For

was one

of the

—

for example, viral or bacobstruction of the trachea by a

result of external factors

many

worst

years, bacterial

killers in the

pneumonia

United

States.

Chapter 22

Antibiotics have greatly decreased its lethality, but it is still a dangerous disease, particularly in the elderly.

By

far

the

most problematic diseases at present

COPD, asthma, lung and newly diagnosed tuberculosis cases in

are those described earlier: cancer,

AIDS

patients.

•

The maximum amount

oxygen we can use during aerobic metabolism, Vo 2mix declines about of

,

9% per decade in inactive people beginning in their mid-20s. In those that remain active, Vo 2max still declines but much less. As we age, the thoracic wall becomes more rigid and the lungs gradually lose their elasticity, resulting in a decreasing ability to ventilate the lungs. Vital capacity declines

by about

0

one-third by the age of 70. Blood 2 levels decline slightly and sensitivity to the stimulating effects of

C0 2

decreases, particularly in a reclining or supine

As a result, many old people tend to become hypoxic during sleep and exhibit sleep apnea position.

(temporary cessation of breathing during

sleep).

The number

The Respiratory System

of glands in the nasal

873

mucosa

de-

creases as does blood flow to this mucosa. Thus, the

nose dries and produces a thick mucus that makes us want to clear our throat. Additionally, many of the respiratory system's protective mechanisms become less effective with age. Ciliary activity of the mucosa decreases, and the macrophages in the lungs become sluggish. The net result is that the elderly are more at risk for respiratory tract infections, particularly pneumonia and influenza. *

Lungs, bronchial vessels

*

tree, heart,

it-

and connecting blood

— together, these organs fashion a remarkable

system that ensures that blood is oxygenated and reand that all tissue cells have access to these services. Although the cooperation of the respiratory and cardiovascular systems is obvious, all organ systems of the body depend on the lieved of carbon dioxide

functioning of the respiratory system, as rized next in Making Connections.

summa-

874

Maintenance of the Body

Unit IV

MAKING CONNECTIONS

SYSTEMS CONNECTIONS: Homeostatic

Interrelationships

Between the Respiratory System and Other Body Systems

Nervous System Respiratory system provides oxygen

normal neuronal

activity;

needed

for

disposes of carbon dioxide

Medullary and pons centers regulate respiratory rate and depth; stretch receptors in lungs provide feed-

back Endocrine System Respiratory system provides oxygen; disposes of carbon dioxide Epinephrine dilates the bronchioles; testosterone promotes laryngeal enlargement in pubertal males;

glucocorticoids promote surfactant production; cate-

cholamines sensitize peripheral chemoreceptors Cardiovascular System Respiratory system provides oxygen; disposes of carbon dioxide; carbon dioxide present in blood as HCC>3~ and H 2 C0 3 contributes to blood buffering Blood is the transport medium for respiratory gases

Lymphatic System/Immunity Respiratory system provides oxygen; disposes of carbon dioxide; tonsils in pharynx house immune cells

Lymphatic system helps to maintain blood volume required for respiratory gas transport;

tem protects

Integumentary System

immune

sys-

respiratory organs from bacteria, bac-

terial toxins, viruses,

and cancer

Respiratory system provides oxygen; disposes of

carbon dioxide

Digestive System

Skin protects respiratory system organs by forming

Respiratory system provides oxygen; disposes of

surface barriers

carbon dioxide Skeletal

Digestive system provides nutrients

System

needed by

res-

piratory system organs

Respiratory system provides oxygen; disposes of

carbon dioxide

Urinary System

Bones protect lungs and bronchi by enclosure Muscular System Respiratory system provides oxygen

needed

for

Respiratory system provides oxygen; disposes of carbon dioxide Kidneys dispose of metabolic wastes of respiratory system organs (other than carbon dioxide)

muscle activity; disposes of carbon dioxide Activity of the

diaphragm and intercostal muscles volume changes that lead to

Reproductive System

essential for producing

pulmonary

ventilation; regular exercise increases

respiratory efficiency

Respiratory system provides oxygen; disposes of carbon dioxide

CLOSER

THE RESPIRATORY SYSTEM and

CONNECTIONS Every day

we

and exhale nearly 20,000

inhale

L of

In

air.

—

it supplies the body with This accomplishes two things the oxygen it needs to oxidize food and release energy, and it expels carbon dioxide, the major waste product

As

of that process.

Interrelationships with the Cardiovascular,

Lymphatic/Immune, and Muscular Systems

crucial as

breathing

is,

most of us

production of angiotensin converting cells of the alveoli plays an

turn,

enzyme by the type important role

in

I

blood pressure regulation.

Lymphatic System/Immunity

don't think very often about the importance of having fresh air is

on

But the

call.

phenomenon

of gulping for

air

familiar to every athlete. Indeed, the respiratory rate

swimmer may jump to over 40 breaths/min and the amount of air inhaled per breath may soar from the usual 500 ml to as much as 6 to 7 L. The respiratory system is beautifully engineered for its function. Its alveoli are flushed with new air more of a competitive

than 15,000 times each day and the alveolar walls are so indescribably thin that red blood cells moving

through the pulmonary capillaries can make the gaseous "swaps" with the air-filled alveoli within a fraction of a second. Although every cell in the body depends on this system for the oxygen it needs to live, the respiratory system interactions that we will consider single-file

here are those

it

has with the cardiovascular, lymphatic,

and muscular systems.

all body systems, only the respiratory system is completely exposed to the external environment (yes,

Of

is exposed but its exposed parts are all dead). Because air contains a rich mix of potentially dangerous inhabitants (bacteria, viruses, fungi, asbestos fibers, etc.), the respiratory system is continuously at risk for infection or damage from external agents. Lymphoid outposts help protect the respiratory tract and enhance the defenses (cilia, mucus) that the respiratory system itself erects. Particularly well situated to apprehend

the skin

intruders at the oral-nasal-pharynx junction are the

and tubal tonsils. Their macrophages engulf foreign antigens and they provide sites where lymphocytes are sensitized to mount immune responses. Their effectiveness is revealed by the fact that respiratory tract infections are much more frequent in people who have had their tonsils removed. palatine, pharyngeal, lingual,

Cardiovascular System

The

interaction

cular systems

between the

and cardiovasso intimate that these two systems are

is

respiratory

inseparable. Respiratory system organs, as important as

they are, can

make

those that occur

depend on the

in

only the external gas exchanges,

body cells provide needed

the lungs. Although

respiratory system to

all

Muscular System Skeletal

muscle

cells, like

other body

cells,

need oxy-

gen to live. The notable part of most respiratory compensations

this interaction

increased muscular

difficult

incidents

where

this

activity. is

(It

is

that

that occur service

is

not the case

to think of

— the exceptions

When we

oxygen, they pick up that oxygen not from the lungs

concern disease conditions.)

but from the blood. Thus, without blood to act as the intermediary and the heart and blood vessels to act as

respiratory system operates at basal levels, but any

the hardware to

pump

the blood around the body,

all

the efforts of the respiratory system would be useless.

are at rest, the

time physical activity becomes more vigorous, the respiratory rhythm picks up the beat to match supply to need and maintain the acid-base balance of the blood.

CLINICAL

CONNECTIONS Respiratory System

4.

Assuming

that Barbara survives,

dent affect her

Case study: Barbara Joley was in the bus that was hit broadside. When she was freed from the wreckage, she was deeply cyanotic and her respiration had stopped. Her heart was still beating, but her pulse was fast and thready. The emergency medical technician reported that when Barbara was found, her head was cocked at a peculiar angle and it looked like she had a fracture at the level of the C 2 vertebra. The following questions

lifestyle in

how

will

her acci-

the future?

Barbara survived transport to the hospital and notes

recorded

at

admission included the following observa-

tions.

Right thorax compressed; ribs 7 to 9 fractured Right lung atelectasis Relative to these notes: 5.

refer to these observations.

What

is

atelectasis

and why

is

only the right lung

affected?

How

might the "peculiar" head position explain Barbara's cessation of breathing? 1.

2.

What procedures

initiated 3.

Why

(do you think) should have been

immediately by the emergency personnel? is

6. 7.

How do

the recorded injuries relate to the atelectasis?

What treatment will be done to reverse the What is the rationale for this treatment 7

atelecta-

sis?

Barbara cyanotic? Explain cyanosis.

(Answers

in

Appendix

F)

876

Unit IV

Maintenance of the Body

Related Clinical Terms Adenoidectomy (adenotonsillectomy) an infected pharyngeal

Surgical removal of

tonsil (adenoids).

Adult respiratory distress syndrome (ARDS) A dangerous lung condition that can develop after severe injury to the body. Following the trauma, neutrophils leave the body's capillaries in large numbers and then secrete chemicals that increase capillary permeability.

The

capillary-rich lungs are

As the lungs fill with the fluids of edema, the patient suffocates. Even with mechanical ventilation, ARDS is hard to control and often lethal. heavily affected.

(as"pi -ra'shun) The act of inhaling or drawing 1 something into the lungs or respiratory passages. Pathological aspiration in which vomit or excessive mucus is drawn into the lungs may occur when a person is unconscious or anesthetized; turning the head to one side is preventive. (2) Withdrawal of fluid by suction (use of an aspirator); done during surgery to keep an area free of blood or other body fluids; mucus is aspirated from the trachea of tracheotomy patients.

Aspiration

(

)

Bronchoscopy [scopy = viewing) Use of a viewing tube inserted through the nose or mouth to examine the internal surface of the main bronchi in the lung. Forceps attached to the tip of the tube can remove trapped objects or take samples of

mucus

for

examination.

Cheyne-Stokes breathing (chan'stoks) Abnormal breathing pattern sometimes seen just before death (the "death rattle") and in people with combined neurological and cardiac disorders. It consists of bursts of tidal volume breaths (increasing and then decreasing in depth) alternating with periods of apnea. Trauma and hypoxia of the brain stem centers, as well as Pco, imbalances between arterial blood and cerebrospinal

Nasal polyps Mushroomlike benign neoplasms of the nasal mucosa; may occur in response to nasal irritation and may block airflow.

Orthopnea (or"thop-ne'ah ortho = ;

ity to

straight, upright) Inabil-

breathe in the horizontal (lying down) position.

Otorhinolaryngology (o"to-ri"no-lar"in-gol'o-je; oto = ear; = nose) Branch of medicine that deals with diagnosis and treatment of diseases of the ears, nose, and throat.

rhino

Pneumonia

Infectious inflammation of the lungs, in which accumulates in the alveoli; the sixth most common cause of death in the United States. Most of the more than 50 different varieties of pneumonia are viral or bacterial. fluid

Pulmonary embolism Obstruction

of the

pulmonary

artery

branches by an embolus (most often a blood clot that has been carried from the lower limbs and through or one of

its

the right side of the heart into the pulmonary circulation). Symptoms are chest pain, productive bloody cough, tachy-

and rapid, shallow breathing. Can cause sudden death unless treated quickly,- usual treatment is oxygen by mask, morphine to relieve pain and anxiety, and anticoagulant drugs to help dissolve the clot. cardia,

Stuttering Condition in which the vocal cords of the larynx are out of control and the first syllable of words is repeated in "machine-gun" fashion. The cause is undetermined, but problems with neuromuscular control of the larynx and

emotional factors are suspect. Many stutterers become fluent when whispering or singing, both of which involve a change in the manner of vocalization.

Sudden infant death syndrome (SIDS) Unexpected death

Endotracheal tube A thin plastic tube threaded into the trachea through the nose or mouth; used to deliver oxygen to patients who are breathing inadequately, in a coma, or under

an apparently healthy infant during sleep. Commonly SIDS is one of the most frequent causes of death in infants under one year old. Believed to be a problem of immaturity of the respiratory control centers. Most cases occur in infants placed in a prone position (on their abdomen) to sleep a position which results in hypoxia due to rebreathing exhaled (C0 2 -rich) air. Since 1992, a campaign recommending placing infants on their back to sleep has led to a decline of 40% or more in the incidence of SIDS in

anesthesia.

the U.S.

Epistaxis (ep'T-stak'sis; epistazo = to bleed at the nose) Nosebleed; commonly follows trauma to the nose or excessive nose blowing. Most nasal bleeding is from the highly vascularized anterior septum and can be stopped by pinching the nostrils closed or packing them with cotton.

Tracheotomy (tra"ke-ot'o-me) Surgical opening of the trachea; done to provide an alternate route for air to reach the lungs when more superior respiratory passageways are ob-

fluid,

may

be causative factors.

of

Deviated septum Condition in which the nasal septum takes a more lateral course than usual and may obstruct breathing; often manifests in old age, but

may

also result

from nose trauma.

called crib death,

—

structed (as by food or a crushed larynx).

Chapter Summary warm, and moisten incoming

and respiratory zone where gas ex-

Media study tools that could provide you additional help in reviewing specific key topics of Chapter 22 are referenced below. | | = Interactive Physiology.

filter,

1. Respiration involves four processes: ventilation, external respiration, internal respiration, and transport of respiratory gases in the blood. Both the respiratory system and the cardiovascular system are involved in respiration.

The Nose and Paranasal Sinuses (pp. 829-833) 3. The nose provides an airway for respiration,- warms,

Functional (pp.

Anatomy

of the Respiratory System

829-844)

Respiratory system organs are divided functionally into conducting zone structures (nose to bronchioles), which 2.

air ;

structures (respiratory bronchioles to alveoli),

changes occur.

moistens, and cleanses incoming air and houses the olfac;

tory receptors. 4.

The external nose is shaped by bone and cartilage The nasal cavity, which opens to the exterior, is

plates.

divided by the nasal septum. Paranasal sinuses and nasolacrimal ducts drain into the nasal cavities.

Chapter 22

The Pharynx

The pharynx extends from the base of the skull to the level of Cf,. The nasopharynx is an air conduit; the orophar-

pages 7-9.

5.

ynx and laryngopharynx are common passageways for food and air. Tonsils arc found in the oropharynx and nasophar-

Pulmonary Ventilation: Inspiration and Expiration (pp. 845-847) of

The

6.

833-836)

(pp.

larynx, or voice box, contains the vocal cords.

also provides a patent airway

mechanism

The

7.

to route food

It

and serves as

and

air into

a switching the proper channels.

epiglottis prevents food or liquids

from entering the

respiratory channels during swallowing.

The Trachea

(pp.

The

The Bronchi and Subdivisions: The Bronchial Tree (pp. 838-842) and left main bronchi run into their respective lungs, within which they continue to subdivide into smaller and smaller passageways. right

The terminal

bronchioles lead into respiratory zone

structures: alveolar ducts, alveolar sacs,

Gas exchange occurs membrane.

and

finally alveoli.

in the alveoli, across the respiratory

in the walls increases.

pressures are equalized.

tory Structures, page 6.

The Lungs and Pleurae

The

(pp.

840-844) Each

in the thoracic cavity.

is

The

The pulmonary

When

intrapul-

pressure, gases flow

from the lungs.

MiM

Respiratory System; Topic: Pulmonary Ventilation, pages 3-6, 11-13.

Physical Factors Influencing Pulmonary Ventilation (pp.

847-849)

5. Friction in the air passageways causes resistance, which decreases air passage and causes breathing movements to become more strenuous. The greatest resistance to air flow occurs in the midsize bronchi. 6.

size

Surface tension of alveolar fluid acts to reduce alveolar

and collapse the

This tendency

alveoli.

is

resisted in

7.

Premature infants have problems keeping their lungs owing to the lack of surfactant in their alveoli, re-

inflated

factant

formed

is

late in fetal

syndrome (IRDS).

from the systemic circulation to the lungs, where gas exchange occurs. The pulmonary veins return newly oxygenated (and most venous) blood back to the heart to be distributed arteries carry blood returned

throughout the body. The bronchial arteries provide the nutrient blood supply of the lungs. 15. The parietal pleura lines the thoracic wall and mediastinum; the visceral pleura covers external lung surfaces. Pleural fluid reduces friction during breathing movements.

flexibility of the

penditure.

MM Respiratory System, Topic: Pulmonary Ventilation, pages 14-18.

Respiratory Volumes and Pulmonary Function Tests (pp.

849-851)

The

volumes are tidal, inspiratory reand residual. The four respiratory capacities are vital, functional residual, inspiratory, and total lung. Respiratory volumes and capacities may be measured by spirometry. 9.

four respiratory

serve, expiratory reserve,

10. Anatomical dead space

is

the

air-filled

volume (about

150 ml) of the conducting passageways. If alveoli become nonfunctional in gas exchange, their volume is added to the anatomical dead space, and the sum is the total dead space. 1 1 Alveolar ventilation is the best index of ventilation ciency because it accounts for anatomical dead space. .

MliM Respiratory System; Topic: Anatomy Review: Respiratory Structures, pages 1-5.

Mechanics of Breathing

(pp.

AVR = (TV -

1.

844-845) Intrapulmonary pressure

is the pressure within the pressure is the pressure within the always negative relative to intrapul-

effi-

dead space) x respiratory rate (ml/breath)

844-852)

Pressure Relationships in the Thoracic Cavity (pp.

Sur-

development.

Lung compliance depends on elasticity of lung tissue bony thorax. When either is impaired, expiration becomes an active process, requiring energy ex-

lungs are primarily air passageways/chambers, supported by an elastic connective tissue stroma. 14.

largely passive, occurring as the inspira-

8.

suspended in its own pleural cavity via its root and has a base, an apex, and medial and costal surfaces. The right lung has three lobes,the left has two. 13.

is

monary pressure exceeds atmospheric

and

lungs, the paired organs of gas exchange, flank the

mediastinum

Expiration

sulting in infant respiratory distress

MM Respiratory System; Topic: Anatomy Review: Respira12.

an area

part by surfactant.

11. As the respiratory conduits become smaller, cartilage is reduced in amount and finally lost; the mucosa thins, and

smooth muscle

to

3. Inspiration occurs when the diaphragm and intercostal muscles contract, increasing the dimensions (and volume) of the thorax. As the intrapulmonary pressure drops, air rushes into the lungs until the intrapulmonary and atmospheric

ated.

10.

from an area of higher pressure

tory muscles relax and the lungs recoil.

trachea extends from the larynx to the primary trachea is reinforced by C-shaped cartilage rings, which keep the trachea patent, and its mucosa is cili-

The

travel

lower pressure.

4.

837-838)

The

8.

bronchi.

9.

Gases

2.

ynx.

The Larynx

877

Km Respiratory System; Topic: Pulmonary Ventilation,

833)

(p.

The Respiratory System

The FVC and FEV

tests, which determine the rate at can be expelled, are particularly valuable in distinguishing between obstructive and restrictive disease.

12.

which

VC

air

Nonrespiratory Air Movements

(p.

852)

alveoli. Intrapleural

pleural cavity;

it is

monary and atmospheric

pressures.

13. Nonrespiratory air movements are voluntary or reflex actions that clear the respiratory passageways or express

emotions.

878

Unit IV

Maintenance of the Body

Basic Properties of Gases

(pp.

852-853)

Control of Respiration

1 Gaseous movements in the body occur by bulk flow and by diffusion. .

2. Dalton's

law states that each gas in a mixture of gases exmix-

erts pressure in proportion to its percentage in the total ture.

3.

Henry's law states that the amount of gas that will

1.

Medullary respiratory centers are the inspiratory center and the ventral respiratory group.

(dorsal respiratory group)

dis-

is

Respiratory System; Topic:

inspiratory center

Gas Exchange, pages 1-6. (p.

Factors Influencing Breathing Rate and

853) 3.

Pulmonary

irritant reflexes are initiated

fumes, and pollutants.

Gas Exchanges Between the Blood, Lungs, and (pp. 853-856)

initiated

.

4.

5.

External Respiration: Pulmonary Gas Exchange

854-856)

(p.

Gas Exchange

is

by extreme overinflation of the

a protective reflex

lungs,- it acts to ini-

Emotions, pain, body temperature changes, and other

mic

External respiration is the process of gas exchange that occurs in the lungs. Oxygen enters the pulmonary capillaries; carbon dioxide leaves the blood and enters the alveoli. Factors influencing this process include the partial pressure gradients, the thickness of the respiratory membrane, surface area available, and the matching of alveolar ventilation and pulmonary perfusion.

Internal Respiration: Capillary

inflation (Hering-Breuer) reflex

stressors can alter respiration by acting through hypothala-

1.

Tissues

The

by dust, mucus,

tiate expiration.

Tissues

(pp.

Depth

863-867)

Alveolar gas contains more carbon dioxide and water vapor and considerably less oxygen than atmospheric air. 1

responsible for the rhythmicity of

2. The pontine respiratory group (and perhaps other respiratory centers in the pons) influence the activity of the medullary inspiratory center.

(pp.

Composition of Alveolar Gas

is

breathing.

proportional to the partial pressure of the gas. Solubility of the gas in the liquid and the temperature are other important factors.

MlM

861-867)

Neural Mechanisms and Generation of Breathing Rhythm (pp. 861-863)

The

solve in a liquid

(pp.

in the

856)

centers. Respiration

6.

Important chemical factors modifying baseline respira+ CO2, H and O2.

tory rate and depth are arterial levels of

the tissues.

MM Respiratory System; Topic: Gas Exchange, pages 6-11,

,

7. An increasing Pco, 1S the most powerful respiratory + stimulant. It acts (via release of in the CSF) on the central chemoreceptors to cause a reflexive increase in the rate and depth of breathing. Hypocapnia depresses respiration and results in hypoventilation and, possibly, apnea.

H

8. Arterial

exchange that occurs between the systemic capillaries and the tissues. Carbon dioxide enters the blood, and oxygen leaves the blood and enters 2. Internal respiration is the gas

can also be controlled voluntarily

for short periods.

PQ

levels

,

below 60

mm Hg constitute the hy-

poxic drive. 9.

Decreased pH and a decline in blood P Q act on periphchemoreceptors and enhance the response to CO2. ,

eral

MlM

Respiratory System; Topic: Control of Respiration, pages 6-14.

15-16.

Respiratory Adjustments

Transport of Respiratory Gases by Blood (pp.

Adjustments During Exercise

856-861)

868-869)

(pp. (p.

868)

1 As exercise begins, there is an abrupt increase in ventilation (hyperpnea) followed by a more gradual increase. When exercise stops, there is an abrupt decrease in ventilation fol.

Oxygen Transport

(pp.

856-859)

1. Molecular oxygen is carried bound to hemoglobin in the blood cells. The amount of oxygen bound to hemoglobin depends on the Po, and Pco, °f blood, blood pH, the presence of BPG, and temperature. A small amount of oxygen gas is transported dissolved in plasma. Nitric oxide carried by hemoglobin aids the delivery of Oi and pickup of CO2 in the tissues by causing vasodilation.

Hypoxia occurs when inadequate amounts of oxygen are delivered to body tissues. When this occurs, the skin and mucosae may become cyanotic.

lowed by a gradual decline to baseline values. 2.

P0

,

Carbon Dioxide Transport

CO2

is

(pp.

859-861)

transported in the blood dissolved in plasma,

may

CO2

Accumulation of CO2 leads to decreased pH depletion CO2 from blood leads to increased blood pH.

U\M

;

Respiratory System; Topic:

Gas

remain quite constant during

and proprioceptor inputs

at

High Altitude

(pp.

868-869)

At high altitudes, there is a decrease in arterial Po, and hemoglobin saturation levels because of the decrease in barometric pressure compared to sea level. Hyperventilation helps restore gas exchange to physiological levels. 3.

Long-term acclimatization involves increased erythro-

poiesis.

are mutually beneficial.

4.

pH

contribute.

Adjustments

4.

chemically bound to hemoglobin, and (primarily) as bicarbonate ion in plasma. Loading and unloading of O2 and

and blood

ventilation. Psychological factors

2.

3.

Pco-,/

exercise andlience do not appear to account for changes in

of

Transport, pages 1-15.

Homeostatic Imbalances of the Respiratory System (pp. 869-871) 1. Two major respiratory disorders are COPD (emphysema and chronic bronchitis) and lung cancer; a significant cause is cigarette smoking. A third major disorder is asthma. Tuberculosis is re-emerging as a major health problem.

Chapter 22

Chronic Obstructive Pulmonary Disease

(p.

869-870)

Lung Cancer

2. Emphysema is characterized by permanent enlargement and destruction of alveoli. The lungs lose their elasticity, and expiration becomes an active process.

characterized by excessive mucus production in the lower respiratory passageways, which severely impairs ventilation and gas exchange. Patients may

Chronic bronchitis

3.

become cyanotic

Asthma

(p.

is

as a result of chronic hypoxia.

870)

immune response victims to wheeze and gasp for air as their inflamed respiratory passages constrict. Marked by exacerbations and periods of relief from symptoms.

An

4.

obstructive condition caused by an

that causes

Lung

6.

gens,

is

(pp.

The Respiratory System

870-871)

cancer, promoted by free radicals and other carcinoextremely aggressive and metastasizes rapidly.

Developmental Aspects of the Respiratory System (pp. 871-873) 1. The superior respiratory system mucosa develops from the invagination of the ectodermal olfactory placodes; that of the inferior passageways develops from an outpocketing of the endodermal foregut lining. Mesoderm forms the walls of the respiratory conduits and the lung stroma.

its

Cystic fibrosis (CF), the

2.

disease, results

form Tuberculosis

(p.

870)

Tuberculosis (TB), an infectious disease caused by an airborne bacterium, mainly affects the lungs. Although most infected individuals remain asymptomatic by walling off the bacteria in tubercles, when immunity is depressed disease symptoms ensue. Recent TB increases in AIDS patients and some patients' failure to complete drug therapy have produced multidrug-resistant TB strains.

a chloride channel.

With

3.

come

most common

from an abnormal

The

clogs respiratory passages

5.

879

age, the thorax

less elastic,

and

result

and

fatal hereditary protein that fails to thick mucus which

CFTR is

invites infection.

becomes more

rigid,

the lungs be-

vital capacity declines. In addition,

the stimulatory effect of increased arterial levels of carbon dioxide is less apparent, and respiratory system protective

mechanisms

are less effective.

Review Questions Multiple Choice/Matching

Most oxygen carried in the blood is (a) in solution in (b) combined with plasma proteins, (c) chemically combined with the heme in red blood cells, (d) in solu10.

(Some questions have more than one correct answer.

Select

the best answer or answers from the choices given.)

the plasma,

tion in the red blood cells.

Cutting the phrenic nerves will result in (a) air entering the pleural cavity, (b) paralysis of the diaphragm, (c) stimulation of the diaphragmatic reflex, (d) paralysis of the epiglot1.

11

.

(b)

tis.

Following the removal of his larynx, an individual would (a) be unable to speak, (b) be unable to cough, (c) have difficulty swallowing, (d) be in respiratory difficulty 2.

by

inflation reflex

12. In

The

detergent-like substance that keeps the alveoli it

is

(b) bile, (c)

surfactant,

(d)

is

called

(a)

temperature, molecule. 6.

(c)

When

(d)

molecular weight and size of the gas

(a)

the size the size of

(b)

The

nutrient blood supply of the lungs is provided by arteries, (b) the aorta, (c) the pulmonary veins, (d) the bronchial arteries.

(a)

Oxygen and carbon dioxide are exchanged in the lungs and through all cell membranes by (a) active transport, (b) 8.

filtration, (d)

osmosis.

(b)

carbon monoxide poisoning, patient, (d) eupnea.

(c)

of

of the following statements are correct?

Expansion of the victim's lungs is brought about by blowing air in at higher than atmospheric pressure

During

inflation of the lungs, the intrapleural pres-

This technique

will not

work

(4)

if

the victim has a the lungs are intact.

if

Expiration during this procedure depends on the and thoracic walls.

(a) all

13.

of these,

(b) 1, 2, 4, (c)

1, 2, 3, (d)

A baby holding its breath will

(a)

1, 4.

have brain

cells

dam-

aged because of low blood oxygen levels, (b) automatically start to breathe again when the carbon dioxide levels in the blood reach a high enough value, (c) suffer heart damage because of increased pressure in the carotid sinus and aortic arch areas, (d) be called a "blue baby." 14. Under ordinary circumstances, which of the following blood components is of no physiological significance? (a) bicarbonate ions, (b) carbaminohemoglobin, (c) nitrogen, (d) chloride.

15. Damage to which of the following would result in cessation of breathing? (a) the pontine respiratory group, (b) the medulla, (c) the stretch receptors in the lungs, (d) the ap-

neustic center.

Which of the following would not normally be treated by 100% oxygen therapy? (Choose all that apply.) (a) anoxia, 9.

emphysema

oxygen,

elasticity of the alveolar

the inspiratory muscles contract,

(c)

(3)

lecithin,

pulmonary

diffusion,

Which

hole in the chest wall, even

the thoracic cavity is increased in length, (c) the volume of the thoracic cavity is decreased, (d) the size of the thoracic cavity is increased in both length and diameter. 7.

(a)

willpower.

sure increases.

reluctant.

of the thoracic cavity is increased in diameter,

the

(2)

from

5. Which of the following determines the direction of gas movement? (a) solubility in water, (b) partial pressure gradi-

ent,

(d)

(positive-pressure breathing).

reduces the surface

tension of the water film in the alveoli

calcium,

mouth-to-mouth artificial respiration, the rescuer from his or her own respiratory system into that

the victim.

the inspiratory center, (b) ventral respiratory group, (c) overinflation of the alveoli and bronchioles, (d) the pontine respiratory group. 4.

(c)

air

(a)

collapsing between breaths because

respiratory center in the brain?

carbon dioxide,

(1)

Under ordinary circumstances, the

3.

of the following has the greatest stimulating

on the

blows

or arrest.

initiated

Which

effect

respiratory crisis in

an

16.

The bulk

of carbon dioxide

is

carried

(a)

chemically

combined with the amino acids of hemoglobin as carbaminohemoglobin in the red blood cells, (b) as the ion HCO3" in the plasma after first entering the red blood cell,

880 (c)

Unit IV

Maintenance of the Body

as carbonic acid in the plasma,

with the

heme

(d)

chemically combined

Thinking and Clinical Application Critical

portion of Hb.

Short Answer Essay Questions

Questions

from the external nares to an subdivisions of organs where applicable, and differentiate between conducting and respiratory zone 17. Trace the route of air

alveolus.

Name

structures.

18. (a) Why is it important that the trachea is reinforced with cartilage rings? (b) Of what advantage is it that the rings are incomplete posteriorly? 19. Briefly explain the anatomical "reason" have deeper voices than boys or women.

why most men (a)

ways? 21. Describe the functional relationships between volume changes and gas flow into and out of the lungs.

22. What is it about the structure of the respiratory membrane that makes the alveoli ideal sites for gas exchange? 23. Discuss

how

24.

(a)

airway resistance, lung compliance, and

Differentiate clearly

ume and

pulmonary

ventilation.

between minute respiratory

alveolar ventilation rate,

more accurate measure

(b)

Which

vol-

provides a

of ventilatory efficiency,

and why?

25. State Dalton's law of partial pressures and Henry's law.

Define hyperventilation, (b) If you hyperventilate, do you retain or expel more carbon dioxide? (c) What effect does hyperventilation have on blood pH? 26.

.

Harry, the

2.

A member of the

gency room

20. The lungs are mostly passageways and elastic tissue, What is the role of the elastic tissue? (b) Of the passage-

alveolar surface tension influence

swimmer with the fastest time on the SpringCollege swim team, routinely hyperventilates before a meet, as he says, "to sock some more oxygen into my lungs so I can swim longer without having to breathe." First of all, what basic fact about oxygen loading has Harry forgotten (a lapse leading to false thinking) ? Second, how is Harry jeopardizing not only his time but his life? 1

field

(a)

27. Describe age-related changes in respiratory function.

"Blues" gang

after receiving a knife

was rushed

wound

into

an emer-

in the left side of

The diagnosis was pneumothorax and a collapsed lung. Explain exactly (a) why the lung collapsed, and (b) why only one lung (not both) collapsed. his thorax.

A surgeon removed three adjacent bronchopulmonary segments from the left lung of a patient with TB. Almost half of the lung was removed, yet there was no severe bleeding, and relatively few blood vessels had to be cauterized (closed off). Why was the surgery so easy to perform? 3.

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The Digestive Sy

PART 1: OVERVIEW OF THE DIGESTIVE SYSTEM (pp. 882-888)

10. Describe the composition of

the importance of each

and differentiate between organs the alimentary canal and

component of

accessory digestive organs. 2. List

and define the major

processes occurring during digestive system activity.

Describe the location and function of the peritoneum.

Define retroperitoneal and

name

the retroperitoneal

organs. 4.

components, and indicate

Describe the function of the digestive system,

3.

(pp.

activity.

11. Explain regulation of gastric

2:

888-925)

Describe the anatomy and basic function of each organ

and accessory organ

of the

alimentary canal. Explain the dental formula and

between deciduous and permanent differentiate clearly

teeth. 7.

and stomach

secretion motility.

12. Describe the function of local intestinal

hormones.

13. State the roles of bile

and

of

pancreatic juice in digestion. 14. Describe

how entry

of

pancreatic juice and bile into

large intestine,

is

regulated.

and describe

the regulation of defecation.

PART 3: PHYSIOLOGY OF CHEMICAL DIGESTION AND ABSORPTION (pp.

925-932)

16. List the

6.

stomach

15. List the major functions of the

FUNCTIONAL ANATOMY OF THE DIGESTIVE SYSTEM PART

in

the small intestine

Describe the tissue

composition and the general function of each of the four layers of the alimentary canal.

5.

the cell

types responsible for secreting its

1.

name

gastric juice,

enzymes involved

chemical digestion;

name

in

the

on which they act and the end products of protein, fat, carbohydrate, and foodstuffs

nucleic acid digestion. 17. Describe the process of

absorption of digested foodstuffs that occurs in the

Describe the composition and

small intestine.

functions of saliva, and explain

how 8.

9.

chewing and swallowing.

Developmental Aspects of the Digestive System (pp. 932-933)

Identify structural

18. Describe

salivation

is

regulated.

Describe the mechanisms of

modifications of the wall of the

stomach and small intestine that enhance the digestive

process in these regions.

embryonic development of the digestive system.

19. Describe abnormalities of the gastrointestinal tract at different stages of

life.

882

Unit IV

Maintenance of the Body

Tongue Parotid gland

Mouth

Sublingual gland

(oral cavity)

-Salivary

glands

Submandibular gland

Pharynx

Esophagus

Stomach Pancreas (Spleen)

Liver

Gallbladder

Transverse colon

Small

—

Duodenum

Descending colon

Jejunum

intestine

Ascending

Ileum

^

>

colon

1

'

i

I

— Large

Cecum

intestine

Sigmoid colon

Rectum Vermiform appendix

Anal

Anus

canal

FIGURE

23.1

Alimentary canal and related accessory digestive organs. (See A

Brief Atlas of the

Human

Body,

Figure 56a.)

Children

are fascinated by the workings of the

They relish crunching a potato chip, delight in making "mustaches" with milk, and giggle when their stomach "growls." As adults, we know that a healthy digestive system digestive system.

is

essential to maintaining

life,

because

it

converts

foods into the raw materials that build and fuel our body's cells. Specifically, the digestive system takes in food, breaks it down into nutrient molecules, absorbs these molecules into the bloodstream, and then rids the body of the indigestible remains.

PART 1: OVERVIEW OF THE DIGESTIVE SYSTEM The organs of the digestive system (Figure 23.1) fall into two main groups: (1) those of the alimentary canal (al"i-men'tar-e; aliment = nourish) and (2) accessory digestive organs. The alimentary canal, also called the gastrointestinal (GI) tract, is the continuous, muscular digestive tube that winds through the body. It digests food breaks it down into smaller fragments [digest = dissolved) and absorbs the digested fragments

—

—

Chapter 23

The Digestive System

883

through its lining into the hlood. The organs of the alimentary canal are the mouth, pharynx, esophagus, stomach, small intestine, and large intestine. The large intestine leads to the terminal opening, or anus. In a cadaver, the alimentary canal is approximately (about 30 feet) long, but in a living person, it is 9 considerably shorter because of its muscle tone. Food material in this tube is technically outside the body because the canal is open to the external environment at both ends. The accessory digestive organs are the teeth,

m

tongue, gallbladder, and a number of large digestive the salivary glands, liver, and pancreas. The glands teeth and tongue are in the mouth, or oral cavity, while the digestive glands and gallbladder lie outside

—

GI

the

tract

and connect

to

it

by ducts. The acces-

sory digestive glands produce a variety of secretions that contribute to the

breakdown

of foodstuffs.

Digestive Processes The

digestive tract can be viewed as a "disassembly

line" in

which food becomes less complex at each and its nutrients become available

step of processing

The processing of food by the digestive system involves six essential activities: ingestion, propulsion, mechanical digestion, chemical digestion, absorption, and defecation (Figure 23.2). to the body.

1.

Blood fe^

vessel

intestine

Ingestion is simply talcing food into the digestive usually via the mouth.

tract,

2.

Propulsion, which moves food through the alicanal, includes swallowing, which is initi-

Defecation

mentary

ated voluntarily, and peristalsis (per"i-stal'sis), an

involuntary stalsis

=

process.

Peristalsis

[peri

= around;

major means of propulwaves of contraction and

constriction), the

sion, involves alternate

FIGURE 23.2

Gastrointestinal tract activities.

Gastrointestinal tract activities include ingestion, mechanical

relaxation of muscles in the organ walls (Figure 23.3a).

digestion, chemical (enzymatic) digestion, propulsion,

main effect is to squeeze food along but some mixing occurs as well. In fact,

absorption, and defecation. Sites of chemical digestion are

Its

the tract, peristaltic

waves are so powerful that, once swallowed, food and fluids will reach your stomach even if you stand on your head.

Mechanical digestion physically prepares food for chemical digestion by enzymes. Mechanical processes include chewing, mixing of food with saliva by the tongue, churning food in the stomach, and segmentation, or rhythmic local constrictions of the intestine (Figure 23.3b). Segmentation mixes food with digestive juices and increases the efficiency of absorption by repeatedly moving different parts of the food mass over the intestinal

produce enzymes or that receive enzymes or made by accessory organs outside the alimentary canal. The mucosa of the GI tract secretes mucus, which protects and lubricates. also sites that

other secretions

3.

Chemical digestion of foodstuffs begins in the mouth and is essentially complete in the small intestine. 5.

Absorption

is

the passage of digested end prod-

ucts (plus vitamins, minerals, and water) from the

lumen

through the mucosal cells by active or passive transport into the blood or lymph. The small intestine is the major absorptive site. of the

GI

tract

wall. 4.

Chemical digestion is a series which complex food molecules

of catabolic steps

are broken down chemical building blocks by enzymes secreted into the lumen of the alimentary canal. in

to their

6. Defecation eliminates indigestible substances from the body via the anus in the form of feces.

Some

of these processes are the job of a single

organ. For example, only the

mouth

ingests

and only

j

884

Unit IV

Maintenance of the Body

From mouth

an optimal environment for its functioning (cavity) of the GI tract, an area that is actually outside the body, and essentially all diges-

creates

in the

lumen

tive tract regulatory

mechanisms

act to control lu-

minal conditions so that digestion and absorption can occur there as effectively as possible. Two facts apply to these regulatory mechanisms: is provoked by a range of chemical stimuli. Sensors fmechanoreceptors and chemoreceptors) involved in 1.

Digestive activity

mechanical controls of

GI

and

tract activity are located in the walls of

the tract organs (Figure 23.4). These sensors respond to several stimuli; the most important are stretching

by food in the lumen, osmolarity (solute pH of the contents, and the presence of substrates and end products of digestion. of the organ

concentration) and

When that

(

1

stimulated, these receptors initiate reflexes activate or inhibit glands that secrete diges-

)

lumen or hormones into the blood or (2) mix lumen contents and move them along the tract by stimulating smooth muscle of the GI tract walls. tive juices into the

Controls of digestive activity are both extrinsic and intrinsic. Many of the controlling systems of the digestive tract are intrinsic a product of "in-house" nerve plexuses or local hormoneproducing cells. The wall of the alimentary canal contains nerve plexuses which extend the entire length of the GI tract and influence each other both in the same and in different digestive organs. As a 2.

—

FIGURE 23.3

Peristalsis

and segmentation,

(a) In

adjacent segments of the intestine (or other

peristalsis,

Sight, smell, taste, thought of food

alimentary tract organs) alternately contract and relax, which

moves food along the tract distally. (b) nonadjacent segments of the intestine and

relax,

In

segmentation,

alternately contract

Central nervous system

moving the food now forward and then backward.

This results

in

1

food mixing rather than food propulsion.

the large intestine defecates. But most digestive system activities require the cooperation of several orbit

by

bit as

Basic Functional Concepts

A theme stressed in this book is

Chemoreceptors, osmoreceptors, or mechanoreceptors

their

own

function.

The

digestive system, however,

Efferent impulses

Local

Effectors:

(enteric)

Smooth

nerve plexus

or gland

-Short

muscle

—

reflexes

3[ Response: Change in

Gastrointestinal

contraction

wall (site of short

Lumen

reflexes)

the body's efforts to internal environment.

maintain the constancy of its Most organ systems respond to changes in that environment either by attempting to restore some plasma variable to its former levels or by changing

—

reflexes

Afferent impulses

food moves along the tract. Later, when we discuss the function of each GI tract organ, we will consider which of these specific processes it performs and the neural or hormonal factors that regulate these processes.

gans and occur

Long

Stimulus

of

the alimentary

or secretory activity

canal

FIGURE 23.4

Neural reflex pathways initiated by

stimuli inside or outside the gastrointestinal tract.

Chapter 23

The Digestive System

885

and mediated entirely by the

the body wall. Between the two peritoneums is the peritoneal cavity, a slitlike potential space contain

local (enteric) plexuses (the so-called gut brain) in

ing fluid secreted by the serous membranes. The serous fluid lubricates the mobile digestive organs, allowing them to glide easily across one another and along the body wall as they carry out their digestive

result,

two kinds

of reflex activity occur, short

long. Short reflexes are

Long

response to GI ated by stimuli arising inside or outside the GI tract and involve CNS centers and extrinsic autonomic nerves (Figure 23.4). The stomach and small intestine also contain tract stimuli.

hormone-producing

cells that,

reflexes are initi-

when

appropriately

stimulated, release their products to the extracellular space.

These hormones

are distributed via blood

different digestive tract organs,

and

same

or

which they prod

to

interstitial fluid to their target cells in the

secrete or contract.

activities.

A

mesentery (mes'en-ter"e) is a double layer of peritoneum a sheet of two serous membranes fused back to back that extends to the digestive organs from the body wall. Mesenteries provide routes for blood vessels, lymphatics, and nerves to reach the digestive viscera; hold organs in place; and store fat. In most places the mesentery is dorsal and attaches to the posterior abdominal wall, but there are

—

—

ventral mesenteries as well (Figure 23.5a).

Digestive System Organs: Relationship and Structural Plan Relationship of the Digestive Organs to the Peritoneum Most

system organs reside in the abdominopelvic cavity. Recall from Chapter 1 that all ventral body cavities contain slippery serous membranes. The peritoneum of the abdominopelvic digestive

most extensive of these membranes (Figure 23.5a). The visceral peritoneum covers the external surfaces of most digestive organs and is continuous with the parietal peritoneum that lines cavity

is

the

(a)

canal organ

Transverse section of abdominal cavity

FIGURE 23.5

(b)

The peritoneum and the peritoneal

Some organs become

cavity, (a) Simplified cross

sections through the abdominal cavity showing the relative locations of the visceral

and

parietal peritoneums,

and dorsal

(left)

and

ventral (right) mesenteries.

Note that

much smaller than depicted here, as it is nearly filled by organs within (b) Some alimentary canal organs lose their mesentery during development and become retroperitoneal.

the peritoneal cavity it.

is

of

the mesenteries, or peritoneal folds, are given specific names (such as the omenta), as described later. Not all alimentary canal organs are suspended by a mesentery. For example, some parts of the small intestine adhere to the dorsal abdominal wall (Figure 23.5b). In so doing, they lose their mesentery and come to lie posterior to the peritoneum. These organs, which include most of the pancreas and parts of the large intestine, are called retroperitoneal organs [retro = behind). By contrast, digestive organs (like the stomach) that keep their mesentery and remain in the peritoneal cavity are called intraperitoneal or peritoneal organs.

canal organ

cavity

Some

the

a retroperitoneal position retroperitoneal

— 886

Unit IV

^(J)^

Maintenance of the Body

HOMEOSTATIC IMBALANCE

and stomach, and the mesenteric arterand inferior) that serve the small and large intestines (see pp. 752 and 755) normally receives one-quarter of the cardiac output. This percentage (blood volume) increases after a meal has been eaten. The hepatic portal circulation (described on pp. 764-765) collects nutrient-rich venous blood draining from the digestive viscera and delivers it to spleen,

liver,

ies (superior

inflammation of the peritoneum, can from a piercing abdominal wound or from a

Peritonitis, or

arise

perforating ulcer that leaks

peritoneal cavity, but a burst all

appendix

stomach

juices into the

most commonly it

results

from

(that sprays bacteria-containing feces

over the peritoneum). In peritonitis, the peritoneal

coverings tend to stick together around the infection

liver. The liver collects the absorbed nutrients for metabolic processing or for storage before releasing them back to the bloodstream for general cellular use.

the

This localizes the infection, providing time for macrophages to attack to prevent the inflammation from spreading. If peritonitis becomes widespread within the peritoneal cavity, it is dangerous and often lethal. Treatment includes removing as much infectious debris as possible from the peritoneal cavity and administering megadoses of antibiotics. • site.

Histology of the Alimentary Canal a share of the work of helps to consider structural characteristics that promote similar functions in all parts of the alimentary canal before we con-

Each digestive organ has only digestion. Consequently,

Blood Supply: The Splanchnic

From

anatomy of the digestive system. the esophagus to the anal canal, the walls

have the same four basic laymucosa, submucosa, muscularis externa, and serosa each containing a predominant tissue type that plays a specific role in food breakdown. of the alimentary canal

The splanchnic

circulation includes those arteries that branch off the abdominal aorta to serve the digestive organs and the hepatic portal circulation.

ers,

—

supply the hepatic, splenic, and left branches of the celiac trunk that serve the

arterial

gastric

it

sider the functional

Circulation

The

—

or tunics (Figure 23.6)

—

nerve plexuses: Myenteric nerve plexus Submucosal nerve plexus

Intrinsic • •

Gland

in

submucosa

Mucosa: •

Epithelium

•

Lamina propria

•

Muscularis

mucosae

Submucosa

Muscularis externa: Longitudinal muscle Circular

muscle

Serosa: Epithelium

Connective tissue

Lumen Mesentery

Duct

of

gland

outside alimentary canal

FIGURE 23.6

Basic structure of the alimentary canal.

the mucosa, submucosa, muscularis externa, and serosa.

Its

four basic layers are

•Mucosa-associated lymphoid tissue

Chapter 23

The Mucosa The mucosa, most

lines the

—

mucous membrane the innermoist epithelial membrane that alimentary canal lumen from mouth to

layer

—

or

is

a

major functions are 1 secretion of mucus, digestive enzymes, and hormones, (2) absorption of the end products of digestion into the blood, and (3) anus.

Its

(

all

region of the

GI

tract

The mucosa

in

may express one or

three of these capabilities.

More complex than most other mucosae in the body, the typical digestive mucosa consists of three sublayers:

(1)

a lining epithelium,

(2)

a

lamina pro-

and (3) a muscularis mucosae. Typically, the epithelium of the mucosa is a simple columnar pria,

epithelium rich in mucus -secreting goblet cells. The slippery mucus it produces protects certain digestive organs from being digested themselves by enzymes working within their cavities and eases food passage along the tract. In the stomach and small intestine, the mucosa also contains both enzyme-secreting and hormone-secreting cells. Thus, in such sites, the mucosa is a diffuse kind of endocrine organ as well as part of the digestive organ. The lamina propria [proprius = one's own), which underlies the epithelium, is loose areolar connective tissue. Its capillaries nourish the epithelium and absorb digested nutrients. Its isolated lymph nodules, part of MALT, the mucosa-associated lymphatic tissue described on p. 782, help defend us against bacteria and other pathogens, which have rather free access to our digestive tract. Particularly

lymphoid follicles occur within the pharynx (as the tonsils) and in the appendix. External to the lamina propria is the muscularis mucosae, a scant layer of smooth muscle cells that produces local movements of the mucosa. For example, twitching of this muscle layer dislodges food particles that have adhered to the mucosa. In the small large collections of

intestine, folds that

throws the mucosa into a series of small immensely increase its surface area.

it

The Submucosa The submucosa, just

external to the mucosa,

is

a

moderately dense connective tissue containing blood and lymphatic vessels, lymphoid follicles, and nerve fibers. Its rich supply of elastic fibers enables the stomach to regain its normal shape after temporarily storing a large meal. Its extensive vascular network supplies surrounding tissues of the GI tract wall.

In several places along the tract, the circular layer thickens, forming sphincters that act as valves to prevent backflow and control food passage from one

organ to the next.

The Serosa The serosa, the

protective outermost layer of the intraperitoneal organs, is the visceral peritoneum. It is

formed of areolar connective tissue covered with mesothelium, a single layer of squamous epithelial cells.

In the esophagus, which racic instead of the

The Muscularis Externa submucosa is the muscularis externa, also simply called the muscularis. This layer is responsible for segmentation and peristalsis. It Just deep to the

an inner circular layer and an outer longitudinal layer of smooth muscle cells (Figure 23.6).

is

located in the tho-

abdominopelvic

cavity, the serosa

replaced by an adventitia (ad"ven-tish e-ah). The is ordinary fibrous connective tissue that binds the esophagus to surrounding structures. is

adventitia

Retroperitoneal organs have both a serosa (on the side facing the peritoneal cavity) and an adventitia (on the side abutting the dorsal body wall).

Enteric Nervous System of the Alimentary Canal canal has its own in-house nerve by the so-called enteric neurons [enter = gut), which communicate widely with one another to regulate digestive system activity. These enteric neurons constitute the bulk of the two major intrinsic nerve plexuses found in the walls of the alimentary canal: the submucosal and myenteric

The alimentary supply, staffed

nerve plexuses (Figure 23.6). The submucosal nerve plexus occupies the submucosa and chiefly regulates the activity of glands and smooth muscle in the mucosa. The large myenteric nerve plexus (mi-en'ter-ik; "intestinal muscle") lies between the circular and longitudinal layers of smooth muscle of the muscularis externa. Enteric neurons of this plexus provide the major nerve supply to the GI tract wall and control GI tract mobility. Control of the patterns of segmentation and peristalsis is largely automatic, involving local reflex arcs between enteric neurons in the same or different plexuses or (even) organs. The enteric nervous system is also linked to the central nervous system by afferent visceral fibers and by sympathetic and parasympathetic branches (motor fibers) of the autonomic nervous system that enter the intestinal wall and synapse with neurons in the intrinsic plexuses. Thus, digestive activity is also subject to extrinsic controls exerted by autonomic

long reflex arcs. Generally speaking, parasympathetic inputs enhance secretory activity and motility, whereas sympathetic impulses inhibit digestive activities. But the largely independent enfibers

typically has

887

)

protection against infectious disease. a particular

The Digestive System

via

much more

than just way stations for the autonomic nervous system as is the case in other organ systems. Indeed, the enteric nervous teric ganglia are

888

Unit IV

Maintenance of the Body

system contains some 100 million neurons, as

of the related accessory organs,

many

salivary glands,

as the entire spinal cord.

PART 2: FUNCTIONAL ANATOMY OF THE DIGESTIVE SYSTEM Now that we have summarized some points that unify the digestive system organs, we are ready to consider the special structural and functional capabilities of each organ of this system. Most of the dishown

in their normal body posiyou may find it helpful to that illustration from time to time as

gestive organs are

such as the teeth, and tongue, because in the mouth food is chewed and mixed with saliva containing enzymes that begin the process of chemical digestion.

The mouth

also begins the propulsive process

which

through the pharynx and esophagus to the stomach. of swallowing,

carries food

The Mouth and Associated Organs The Mouth The mouth, a mucosa-lined

cavity, is also called the

tions in Figure 23.1, so

oral cavity, or buccal cavity (buk'al). Its boundaries

refer back to you read the following

are the lips anteriorly, cheeks laterally, palate superi-

and tongue inferiorly (Figure 23.7). Its anterior opening is the oral orifice. Posteriorly, the oral cavity is continuous with the oropharynx. The walls of the mouth are lined with stratified squamous epithelium which can withstand considerable friction. The epithelium on the gums, hard palate, and dor-

sections.

orly,

The Mouth, Pharynx, and Esophagus The mouth

is

the only part of the alimentary canal

involved in ingestion. However, most digestive functions associated with the mouth reflect the activity

Opening

Uvula Soft palate

of

sum

of the tongue

is

slightly keratinized for extra

protection against abrasion during eating. Like

moist surface

linings, the oral

all

mucosa responds

to

pharyngotympanic in nasopharynx Superior

Palatoglossal arch

Ol^L

Palatine

lip

Superior labial

tonsil

frenulum

Hard palate Oral cavity Palatoglossal

Lingual tonsi

pharyngeal arch

Oropharynx

Posterior wall Epiglottis of

oropharynx

Lingual

frenulum

Gingivae (gums) Inferior labial

frenulum

FIGURE

23.7

oral cavity

Anatomy

and pharynx,

of the oral cavity (mouth),

(b) Anterior view.

(a) Sagittal

section of the

Chapter 23

injury by producing antimicrobial peptides called defensins,

which helps

to explain

how

the mouth, a

teeming with disease-causing microbes, remains remarkably healthy. so site

The Lips and Cheeks

The

lips (labia)

and the

cheeks have a core of skeletal muscle covered externally by skin. The orbicularis oris muscle forms the fleshy lips; the cheeks are formed largely by the buccinators. The lips and cheeks help keep food between the teeth when we chew and play a small role in speech. The recess bounded externally by the lips and cheeks and internally by the gums and teeth is called the vestibule ("porch").

within the teeth and

The

gums

much

is

The

area that lies

the oral cavity proper.

than most people think; anatomically they extend from the inferior margin of the nose to the superior boundary of the chin. The reddened area where one applies lipstick or lands a kiss is called the red margin. This transitional zone, where keratinized skin meets the oral mucosa, is poorly keratinized and translucent, alloware

lips

larger

ing the red color of blood in the underlying capillaries

show through. The lack of sweat or sebaceous glands in this region means it must be moistened to

with saliva periodically to prevent it from becoming dry and cracked (chapped lips). The labial frenulum (fren'u-lum)

is

a

median

aspect of each lip to the

its

raphe

gated,

(ra'fe),

gum

The

soft palate

The mucosa on

a

grips the food

the bolus posteriorly into the pharynx.

tongue also helps us form consonants

The

versatile

(k, d, t,

and so

when we speak. The tongue has both intrinsic and extrinsic skeletal muscle fibers. The intrinsic muscles are

on)

confined in the tongue and are not attached to bone.

Their muscle

fibers,

which run

in several different

planes, allow the tongue to change its position),

becoming

its

shape (but not

thicker, thinner, longer, or

shorter as needed for speech and swallowing. The extrinsic muscles extend to the tongue from their points of origin on bones of the skull or the soft

Chapter 10 (see Table 10.2 and Figure 10.7). The extrinsic muscles alter the tongue's position; they protrude it, retract it, and move it from side to side. The tongue has a median septum of connective tissue, and each half contains identical muscle groups. A fold of mucosa, called the lingual frenulum, secures the tongue to the floor of the mouth and limits posterior movements of the palate, as described in

tongue.

Children born with an extremely short lingual frenuare often referred to as "tongue-tied" because of speech distortions that result when tongue movement is restricted. This congenital condition, called

lum

ankyloglossia ("fused tongue"),

by snipping the frenulum.

is

corrected surgically

•

either side of

is slightly

corru-

mobile fold formed mostly of

skeletal muscle. Projecting

downward from

its free

the fingerlike uvula (u'vu-lah). The soft palate rises reflexively to close off the nasopharynx when we swallow.

edge

fibers, and during chewing, and constantly repositions it between the teeth. The tongue also mixes food with saliva and forms it into a compact mass called a bolus (bo'lus; "a lump"), and then initiates swallowing by pushing it

HOMEOSTATIC IMBALANCE

to create friction. is

bundles of skeletal muscle

(Figure 23.7b).

a midline ridge,

which helps

889

fold that joins the internal

The Palate The palate, forming the roof of the mouth, has two distinct parts: the hard palate anteriorly and the soft palate posteriorly (see Figure 23.7). The hard palate is underlain by the palatine bones and the palatine processes of the maxillae, and it forms a rigid surface against which the tongue forces food during chewing.

The Digestive System

is

The

superior tongue surface bears papillae, peglike

projections of the underlying

The

mucosa

(Figure 23.8).

conical filiform papillae give the tongue surface

roughness that aids in licking semisolid foods (such as ice cream) and provide friction for manipulating foods in the mouth. These papillae, the smalla

and most numerous type, align in parallel rows on the tongue dorsum. They contain keratin, which stiffens them and gives the tongue its whitish

est

To demonstrate this action, swallow at the same time.

try to breathe

and

anchored to the tongue by the palatoglossal arches and to the wall of the oropharynx by the more posterior palatopharyngeal Laterally, the soft palate is

arches. These two paired folds form the boundaries of the fauces (faw'sez,- fauc = throat), the arched area of the oropharynx that contains the palatine tonsils.

The Tongue The tongue occupies most

when the The tongue is composed

of the oral cavity

Figure 23.7).

mouth and mouth is closed

the floor of the

fills

(see

of interlacing

appearance.

The mushroom-shaped fungiform

papillae are

scattered widely over the tongue surface. Each has a vascular core that gives it a reddish hue. Ten to twelve large circumvallate, or vallate, papillae are located in a V-shaped row at the back of the tongue. They resemble the fungiform papillae but have an additional surrounding furrow. Both the fungiform and circumvallate papillae house taste buds. Immediately posterior to the circumvallate papillae is the sulcus terminalis, a groove that

890

Unit IV

Maintenance of the Body

FIGURE 23.8 locations papillae.

Dorsal surface of the tongue. Also shown are the tonsils, the and detailed structures of the circumvallate, fungiform, and filiform (Top right, 300x; bottom right, 100x.) (See A Brief Atlas of the Human

Body, Figure

36.)

distinguishes the anterior two-thirds of the tongue

vestibule next to the second upper molar. Branches

that lies in the oral cavity from

of the facial nerve

siding in the oropharynx.

its

posterior third re-

The mucosa

root of the tongue lacks papillae, but

covering the

it is still

because of the nodular lingual tonsil, which deep to its mucosa (see Figure 23.8).

The Salivary Glands A number of glands associated with

bumpy

lies just

the oral cavity

mouth, (2) dissolves food chemicals so that they can be tasted, (3) moistens food and aids in compacting it into a bolus, and (4) contains enzymes that begin the chemical breakdown of starchy foods. Most saliva is produced by extrinsic salivary glands that lie outside the oral cavity and empty their secretions into it. Their output is augmented slightly by small intrinsic salivary glands, also throughout the oral

cavity mucosa.

The

paralysis.

homeostatic imbalance

secrete saliva. Saliva (1) cleanses the

called buccal glands, scattered

run through the parotid gland on their way to the muscles of facial expression. For this reason, surgery on this gland can result in facial

compound tubuloalveolar glands that develop from the oral mucosa and remain connected to it by ducts

a common children's disease, is an inflammation of the parotid glands.caused by the mumps virus (myxovirus), which spreads from person to person in saliva. If you check the location of the parotid glands in Figure 23.9a, you can understand why people with mumps complain that it hurts to open their mouth or chew. Besides that discomfort, other signs and symptoms of mumps include moderate fever and pain when swallowing acid foods

Mumps,

(sour pickles, grapefruit juice, fections in adult males carry a

may become

etc.).

Mumps

viral in-

25% risk that the testes

infected as well, leading to

sterility.

•

extrinsic salivary glands are paired

The large parotid gland (pah-rot'id; par = near, otid = the ear) lies anterior to the ear between the masseter muscle and the skin. The promi(Figure 23.9).

nent parotid duct parallels the zygomatic arch, and opens into the

pierces the buccinator muscle,

About the

size of a walnut, the

submandibular

gland lies along the medial aspect of the mandibular body. Its duct runs beneath the mucosa of the oral cavity floor and opens at the base of the lingual frenulum (see Figure 23.7). The small sublingual gland lies anterior to the submandibular gland under

— The Digestive System

Chapter 23 Parotid gland

Serous

891

Serous demilunes

cells

Tongue

Teeth Ducts of sublingual

gland Parotid duct

Masseter muscle Frenulum of tongue

Body

of

mandible

(cut)

Sublingual gland

Posterior belly of digastric

muscle

Submandibular

Mylohyoid muscle (cut)

duct

Submandibular Anterior belly of digastric

gland

muscle

Mucous

cells

(a)

(b)

FIGURE 23.9

The salivary glands,

(a)

The

sublingual salivary glands associated with the

parotid, submandibular,

left

aspect of the oral

and

cavity,

Photomicrograph of the sublingual salivary gland (40x), which is a mixed salivary gland. Mucus-producing cells stain light blue and serous-secreting units stain purple. The serous cells sometimes form demilunes (caps) around the bases of the mucous cells. Copyright© Science Photo Library/Photo Researchers, Inc. (b)

the tongue and opens via 10-12 ducts into the floor

that inhibits bacterial growth in the

mouth. To a greater or lesser degree, the salivary glands are composed of two types of secretory cells: mucous and serous. Serous cells produce a watery secretion containing enzymes, ions, and a tiny bit of mucin, whereas the mucous cells produce mucus, a stringy,

help to prevent tooth decay;

viscous solution. The parotid glands contain only serous cells. The submandibular and buccal glands have approximately equal numbers of serous and mucous cells. The sublingual glands contain mostly

bacteria that live

of the

mucous

cells.

Composition of Saliva Saliva is largely water 97 to 99.5% and therefore is hypo-osmotic. Its osmolarity depends on the precise glands that are active and the nature of the stimulus for salivation. As

—

a rule, saliva

is

slightly acidic

(pH 6.75 to

7.00), but

pH may vary. Its solutes include electrolytes + (Na K + CP, P0 4 and HCO, the digestive

its

,

);

,

,

enzyme

amylase; the proteins mucin (mu'sin), lysozyme, and IgA and metabolic wastes salivary

;

(urea

and uric

glycoprotein

acid).

When

dissolved in water, the

mucin forms thick mucus

that lubri-

and hydrates foodstuffs. Protection against microorganisms is provided by 1 IgA

cates the oral cavity

(

antibodies;

(2)

)

lysozyme, a bacteriostatic enzyme

(3)

mouth and may

a cyanide

compound;

and

(4) defensins (see p. 655.) Besides acting as a local antibiotic, defensins function as cytokines to call

defensive cells (lymphocytes, neutrophils,

the

mouth

etc.)

into

for battle.

In addition to these four protectors, the friendly

on the back

of the tongue convert

food-derived nitrates in saliva into nitrites which, in turn, are converted into nitric oxide in an acid envi-

ronment. This transformation occurs around the gums, where acid-producing bacteria tend to cluster, and in the hydrochloric acid-rich secretions of the stomach. The highly toxic nitric oxide is believed to act as a bactericidal agent in these locations.

Control of Salivation

The

intrinsic salivary

glands secrete saliva continuously in amounts just sufficient to keep the mouth moist. But when food enters the mouth, the extrinsic glands are activated and copious amounts of saliva pour out. The average output of saliva is 1000-1500 ml per day. Salivation is controlled primarily by the parasympathetic division of the autonomic nervous

system. When we ingest food, chemoreceptors and pressoreceptors in the mouth send signals to the salivatory nuclei in the brain stem (pons and

-

892

Maintenance of the Body

Unit IV

incisors Central (6-8 mo) Lateral (8

- 10

Deciduous

.In contrast to parasympathetic controls, the sympathetic division causes release of a thick mucin-rich saliva. Extremely strong activation of the sympathetic division constricts blood vessels serving the salivary glands and almost completely inhibits saliva release, causing a dry mouth. Dehydration also inhibits salivation because low blood volume results in reduced filtration pressure at cap-

(milk) teeth

illary beds.

mo

Canine (eyetooth) (16-20 mo) Molars First

molar

(10-15 mo) Second molar (about 2

•J

yr)

^Ql^ homeostatic imbalance Incisors

Any

disease process that inhibits saliva secretion causes difficulty in talking, swallowing, and eating.

Central (7 yr) Lateral (8

Because decomposing food particles are allowed to accumulate and bacteria flourish, halitosis (hal"i-to'sis "bad breath") can result. •

yr]

;

Canine (eyetooth) (11 yr)

Premolars

The Teeth The teeth lie

(bicuspids) First premolar

in sockets (alveoli) in the gum-covered margins of the mandible and maxilla. The role of the teeth in food processing needs little introduction. We masticate, or chew, by opening and closing our jaws and moving them from side to side while continually using our tongue to move the food between our teeth. In the process, the teeth tear and grind the

(11 yr)

Second premolar (12- 13 yr) Molars First

molar

(6

Second molar (12 - 13 yr)

food, breaking

Third molar

(wisdom tooth)

(17-25

As

nervous sysand impulses sent via motor fibers in the facial (VII) and glossopharyngeal (IX) nerves trigger a dramatically increased output of watery (serous), enzyme-rich saliva. The chemoreceptors are activated most strongly by acidic substances such as vinegar and citrus juice. The pressoreceptors are activated by virtually any mechanical stimulus in the mouth even rubber bands. medulla).

a result, parasympathetic

activity increases

—

Sometimes just the sight or smell of food is enough to get the juices flowing. The mere thought of hot fudge sauce on peppermint stick ice cream will

down

into smaller fragments.

Dentition and the Dental Formula Ordinarily by age 2 1 two sets of teeth, the primary and permanent dentitions, have formed (Figure 23.10). The primary dentition consists of the deciduous teeth (de-sid'u-us,- decid = falling off), also called milk or baby teeth. The first teeth to appear, at about age six months, are the lower central incisors. Additional pairs of teeth erupt at one- to two -month intervals until about 24 months, when all 20 milk teeth have emerged. As the deep-lying permanent teeth enlarge and develop, the roots of the milk teeth are resorbed from below, causing them to loosen and fall out between the ages of 6 and 12 years. Generally, all the teeth of the permanent dentition but the third molars have erupted by the end of adolescence. The third molars, also called the wisdom teeth, emerge between the ages of 1 7 and 25 years. There are usually 32 permanent teeth in a full set, but sometimes the ,

yr)

FIGURE 23.10 Human deciduous and permanent teeth of the lower jaw. Approximate time of tooth eruption is shown in parentheses. The shapes of individual teeth are shown on the right.

tem

it

make many

a

mouth

water! Irritation of the

lower regions of the GI tract by bacterial toxins,

— particularly when feeling of nausea — also increases

spicy foods, or hyperacidity

companied by salivation.

a

This response

neutralize the irritants.

may

ac-

help

wash away

or

wisdom *

i

^J|l%

When

teeth never erupt or are completely absent.

homeostatic imbalance

embedded in the jawbone, it is impacted. said to be Impacted teeth can cause a good deal of pressure and pain and must be removed surgi• cally. Wisdom teeth are most commonly impacted. a tooth remains

Chapter 23

and

The premolars

pierce.

(bicuspids)

cating the

numbers and

relative positions of the dif-

ferent types of teeth in the

\

and

molars have broad crowns with rounded cusps (tips) and are best suited for grinding or crushing. The molars (literally, "millstones"), with four or five cusps, are the best grinders. During chewing, the upper and lower molars repeatedly lock together, an action that generates tremendous crushing forces. The dental formula is a shorthand way of indi-

mouth. This formula

Enamel

Dentin

Crown Dentinal tubules

Pulp cavity (contains

blood vessels

Neck

and nerves)

is

Gingiva

written as a ratio, uppers over lowers, for one-half of the mouth. Since the other side is a mirror image, the total dentition

is

893

Which material forms the bulk of the tooth?

Teeth are classified according to their shape and function as incisors, canines, premolars, and molars (Figure 23.10). The chisel-shaped incisors are adapted for cutting or nipping off pieces of food. The conical or fanglike canines (cuspids or eyeteeth) tear

The Digestive System

(gum)

obtained by multiplying the

2. The primary dentition consists two incisors (I), one canine (C), and two molars (M) on each side of each jaw, and its dental formula

dental formula by

Cementum

of

is

Root-

written as

Root canal

7 PenaW

(

l\\r 9M 21, 1C, 2M

(lower jaw)l

x 2

(20 teeth)

Periodontal

igament

permanent dentition [two incisors, one canine, two premolars (PM), and three molars] is Similarly, the

Apical

21,

1C,

21,

1C,

2PM, 2PM,

3M 3M

x

foramen

2 (32 teeth)

Tooth Structure Each tooth has two major recrown and the root (Figure 23.11). The

Bone

gions: the

enamel-covered crown is the exposed part of the tooth above the gingiva (jin'ji-vah), or gum, which surrounds the tooth like a tight collar. Enamel, an acellular, brittle

FIGURE within

material that directly bears the force

23.1

its

Longitudinal section of a canine tooth

1

bony

alveolus.

of chewing,

is the hardest substance in the body. It is heavily mineralized with calcium salts, and its

the tooth"). This ligament anchors the tooth in the

densely packed hydroxy apatite (mineral) crystals are

bony alveolus

oriented in force-resisting columns perpendicular to the tooth's surface. The cells that produce enamel

a gomphosis.

a tooth,

dips

called the

degenerate when the tooth erupts; consequently, any decayed or cracked areas of the enamel will not heal and must be artificially filled. The portion of the tooth embedded in the jawbone is the root. Canine teeth, incisors, and premolars have one root, although the first upper premolars com-

gingival sulcus. In youth, the gingiva adheres tena-

monly have two. As

tooth" sometimes applied to elderly people. Dentin, a bonelike material, underlies

for molars, the first

two upper

molars have three roots, while the corresponding lower molars have two. The root pattern of the third molar varies, but a fused single root is most common. The crown and root are connected by a constricted tooth region called the neck.

face of the root is covered

The

outer sur-

by cementum, a

calcified

connective tissue, which attaches the tooth to the thin periodontal ligament (per"e-o-don'tal "around ;

of the jaw,

forming a fibrous

joint called

Where the gingiva borders on downward to form a shallow groove

ciously to the

enamel covering the crown. But

it

as the

gums

begin to recede with age, the gingiva adheres to the more sensitive cementum covering the superior region of the root. As a result, the teeth appear to get longer in old age hence the expression "long in the

—

enamel cap and forms the bulk

the

of a tooth. It sur-

rounds a central pulp cavity containing a number of blood vespulp. Pulp sels, and nerve supplies nutrients to the tooth tissues and provides soft tissue structures (connective tissue, fibers) collectively called

894

Unit IV

Maintenance of the Body

Where becomes

for tooth sensation.

into the root,

it

the pulp cavity extends the root canal. At the

proximal end of each root canal is an apical foramen that provides a route for blood vessels, nerves, and other structures to enter the pulp cavity of the tooth. The teeth are served by the superior and inferior alveolar nerves, branches of the trigeminal nerve (see Table 13.2, p. 503) and by the superior and inferior alveolar arteries, branches of the maxillary artery (see Figure 19.20, p. 749).

Dentin contains unique

radial striations called

caljed gingivitis (jin'ji-vi'tis), the

swollen, and is

80-90%

of tooth loss in adults.

gums

down fairly rapidly to compensate for

bone.

laid

tooth damage or decay.

Still,

tooth loss

and consequent darkening commonly caused by a blow to the

pinches off the blood supply to the tooth and the nerve dies. Typically the pulp becomes infected by bacteria some time later and must be removed by roor canal therapy. After the cavity is sterilized and filled with an inert material, the tooth is capped. • jaw. Swelling in the local area

Although enamel, dentin, and cementum are all calcified and resemble bone, they differ from bone in that they are avascular. Enamel also differs from cementum and dentin because it lacks collagen as its main organic component.

Tooth and

Gum

Disease

Dental caries (kar'ez; "rottenness"), or cavities, result from gradual demineralization of enamel and underlying dentin by bacterial action. Decay begins when dental plaque (a film of sugar, bacteria, and other mouth debris) adheres to the teeth. Bacterial metabolism of the trapped sugars produces acids, which can dissolve the calcium

salts of the teeth.

Once

the salts are leached

remaining organic matrix of the tooth is readily digested by protein-digesting enzymes released by the bacteria. Frequent brushing and flossing daily help prevent damage by removing forming plaque. More serious than tooth decay is the effect of unremoved plaque on the gums. As dental plaque accumulates, it calcifies, forming calculus (kal'ku-lus; "stone") or tartar, which disrupts the seals between out, the

the gingivae and the teeth, putting the for infection. In the early stages of

gums

if

the

not inevitable. Even advanced

teeth, cleaning the infected pockets,

to shrink the pockets,

then cutting the

and following up with

antibiotic therapy. Together, these treatments allevi-

and encourage reattachment of the surrounding tissues to the teeth and ate the bacterial infestations

Much less painful

are

(

1

)

a

new laser approach

now

and

(2)

in clinical trials in

a nonsur-

which an

antibiotic-impregnated film is temporarily glued to the exposed root surface. Clinical treatment is fol-

of a tooth's nerve is

is

for destroying the diseased tissues

HOMEOSTATIC IMBALANCE of the tooth

reversible

is

cases of periodontitis can be treated by scraping the

gical therapy

Death

Gingivitis

are red, sore,

removed, but if it is neglected the bacteria eventually invade the bone around the teeth, forming pockets of infection. The immune system attacks not only the intruders but also the body tissues, carving deep pockets around the teeth and dissolving the bone away. This more serious condition, called periodontal disease, or periodontitis, affects up to 95% of all people over the age of 35 and accounts for calculus

dentinal tubules (Figure 23.11). Each tubule contains an elongated process of an odontoblast (o-don'to-blast; "tooth former"), the cell type that secretes and maintains the dentin. The cell bodies of odontoblasts line the pulp cavity just deep to the dentin. Dentin is formed throughout adult life and gradually encroaches on the pulp cavity. New dentin

can also be

may bleed.

gums

at risk

such an infection,

lowed up by a

home regimen

of plaque

removal by

consistent frequent brushing and flossing and hydro-

gen peroxide rinses. Although periodontal disease has traditionally been viewed as a self-limiting low-grade infection, there may be more at risk than teeth. Some contend that

it

increases the risk of heart disease in at least

two ways:

(1)

the chronic inflammation promotes

atherosclerotic plaque formation,

and

(2)

bacteria

entering the blood from infected gums stimulate clot formation that helps to clog coronary arteries.

The Pharynx From

the mouth, food passes posteriorly into the oropharynx and then the laryngopharynx (see Figure 23.7), both ids,

and

The

air.

common passageways for food,

(The nasopharynx has no

flu-

digestive role.)

histology of the pharyngeal wall resembles

The mucosa contains a squamous epithelium with mucus-producing glands. The

that of the oral cavity. friction-resistant

well supplied

stratified

external muscle layer consists of two skeletal muscle layers.

The

Those

of the outer layer, the pharyngeal constrictor

cells of

the inner layer run longitudinally.

muscles, encircle the wall like three stacked fists (see Figure 10.8). Contractions of these muscles propel food into the esophagus below.

The Esophagus The esophagus

(e-sof'ah-gus; "carry food"), a

cular tube about 25

when

cm

mus-

(10 inches) long, is collapsed not involved in food propulsion (Figure 23.12).

Chapter 23

(a)

895

(b)

FIGURE 23.12

Microscopic

region close to the stomach junction, so

structure of the esophagus. (a)

The Digestive System

the muscularis-is

Cross-sectional view of the

esophagus showing its four tunics (5X). The section shown is taken from the

After food

composed

of

simple columnar epithelium of the

stomach (bottom).

Arrow shows the point of abrupt

it is

As shown

in Figure 23.1, the esophagus takes a

fairly straight

course through the mediastinum of

thorax and pierces the diaphragm at the esophageal hiatus (hi-a'tus; "gap") to enter the abthe

domen.

It

joins the

g a/diu/s /Gojsjoas e

se\j\

sji

6uipayaj

'iun//ai/}/da

jeuiun/oo

ipeujojs a^; seajaq/w 'uoi}Duj

ajepoLuiucooe isnuu snip pue ajnip e Ajuieuu sa;e3/pu/ ujni/aipida

-uoiisaBip

snomenbs pey^ejjs

ai/i

si

LjBiLj

sn6eqdosa aqj a^uasajd

p

stomach

at the cardiac orifice.

The cardiac orifice is surrounded by the cardiac or gastroesophageal sphincter (gas"tro-esof"ah-je'al) (see Figure 23. 13),

3\oj /Gojajoas

squamous

muscle, (b) Longitudinal section through

moves through the laryngopharynx,

ui

stratified

the esophagus-stomach junction (80X).

routed into the esophagus posteriorly as the epiglottis closes off the larynx to food entry.

/eo/iuaip

from the

transition

epithelium of the esophagus (top) to the

smooth

That

is, it

which

is

a physiological sphincter.

acts as a valve, but the only structural ev-

idence of this sphincter

is

a slight thickening of the

smooth muscle at that point. The muscular diaphragm, which surrounds this sphincter, helps

circular

keep

it

closed

when

food

is

not being swallowed.

896

Unit IV

Maintenance of the Body

^tQ^ HOMEOSTATIC IMBALANCE Heartburn, the first symptom of gastroesophageal (GERD), is the burning, radiating sub-

reflux disease

sternal pain that occurs

when

the acidic gastric juice

regurgitates into the esophagus.

Symptoms

similar to those of a heart attack that

are so

many

first-

time sufferers of heartburn are rushed to the hospital emergency room. Heartburn is most likely to happen when one has eaten or drunk to excess, and in conditions that force abdominal contents superiorly, such as extreme obesity, pregnancy, and running, which causes stomach contents to splash upward with each step (runner's reflux). It is also common in those with a hiatal hernia, a structural abnormality in which the superior part of the stomach protrudes slightly above the diaphragm. Since the diaphragm no longer reinforces the cardiac sphincter, gastric juice

particularly

when

lying

may

flow into the esophagus, If the episodes are fre-

down.

quent and prolonged, esophagitis (inflammation of the esophagus) and esophageal ulcers may result. An even more threatening sequel is esophageal cancer. However, these consequences can usually be prevented or managed by avoiding late-night snacks and by using antacid preparations •

Digestive Processes Occurring in the Mouth, Pharynx, and Esophagus The mouth and its accessory digestive organs are involved in most digestive processes. The mouth (1) ingests, (2) begins mechanical digestion by chewing, and (3) initiates propulsion by swallowing. Salivary amylase, the enzyme in saliva, starts the chemical breakdown of polysaccharides (starch and glycogen) into smaller fragments of linked glucose molecules. (If you chew a piece of bread for a few minutes, it will begin to taste sweet as sugars are released.) Except for a few drugs that are absorbed through the oral mucosa (for example, nitroglycerine), essentially no absorption occurs in the mouth. In contrast to the multifunctional mouth, the pharynx and esophagus merely serve as conduits to pass food from the mouth to the stomach. Their single digestive function is food propulsion, accomplished by the role they play in swallowing. Since chemical digestion is covered in a special physiology section later in the chapter, only the mechanical processes of chewing and swallowing are discussed here. Mastication (Chewing)

As food Unlike the mouth and pharynx, the esophagus wall has all four of the basic alimentary canal layers described 1.

earlier.

Some

features of interest:

The esophageal mucosa contains a nonkeratmized squamous epithelium. At the esophagus-

stratified

stomach junction, that abrasion-resistant epithelium changes abruptly to the simple columnar epithelium of the stomach, which is specialized for secretion (Figure 23.12b). 2.

When

is empty, its mucosa and thrown into longitudinal folds

the esophagus

submucosa

are

(Figure 23.12a). When food is in transit in the esophagus, these folds flatten out.

The

submucosa contains mucus-secreting esophageal glands. As a bolus moves through the esophagus, it compresses these glands, causing them to secrete mucus that "greases" the esophageal walls 3.

and aids food passage. 4.

The muscularis externa

is

skeletal

muscle in

superior third, a mixture of skeletal and muscle in its middle third, and entirely

muscle in 5.

its

smooth smooth

its inferior third.

Instead of a serosa, the esophagus has a fibrous composed entirely of connective tissue,

adventitia

which blends with surrounding structures along route.

its

mechanical breakdown begins with mastication, or chewing. The cheeks and closed lips hold food between the teeth, the tongue mixes food with saliva to soften it, and the teeth cut and grind solid foods into smaller morsels. Mastication is partly voluntary and partly reflexive. We voluntarily put food into our mouths and contract the muscles that close our jaws. Continued jaw movements are controlled mainly by stretch reflexes and in response to pressure inputs from receptors in the cheeks, gums, and tongue, but they can also be enters the

mouth,

its

voluntary as desired.

Deglutition (Swallowing)

:

To send food on its way from the mouth, it is first compacted by the tongue into a bolus and then swallowed. Deglutition (deg"loo-tish'un), or swallowing, is

a complicated process that involves coordinated

22 separate muscle groups. It has two major phases, the buccal and the pharyngealactivity of over

esophageal.

The buccal phase occurs

in the

voluntary. In the buccal phase,

we

mouth and

is

place the tip of

the tongue against the hard palate, and then contract the tongue to force the bolus into the oropharynx (Figure 23.13a). As food enters the pharynx and stimulates tactile receptors there, it passes out of our control and into the realm of involuntary reflex activity.

Chapter 23

The Digestive System

897

Tongue Pharynx Epiglottis

Glottis

Trachea (a)

Bolus

Upper esophageal

(b)

FIGURE 23.13

swallowing consists of

a

voluntary

and involuntary (pharyngeal-esophageal) phases (b-e). (a) During the buccal phase, the tongue rises and presses against the hard palate, forcing the food bolus into the oropharynx where the involuntary phase of swallowing begins, (b) The uvula and larynx rise to prevent food from entering phase

(c)

Upper esophageal sphincter contracted

Deglutition

(swallowing). The process of (buccal)

Upper esophageal sphincter relaxed

sphincter contracted

Relaxed muscles

1

Relaxed muscles

(a)

respiratory passageways. Relaxation of

Circular

constricting

passageway and pushing

Bolus of food

bolus

muscles contract,

shortening

passageway ahead of bolus

food to enter the esophagus, (c) The constrictor muscles of the pharynx

Gastroesophageal -

food into the esophagus inferiorly, and the upper esophageal sphincter contracts after entry, (d) Food is moved through the esophagus to the stomach by peristalsis, (e) The gastroesophageal sphincter opens, and food enters the stomach.

1

sphincter closed

Stomach

(d)

The involuntary pharyngeal-esophageal phase swallowing is controlled by the swallowing center located in the medulla and lower pons. Motor impulses from that center are transmitted via various cranial nerves, most importantly the vagus nerves, to the muscles of the pharynx and esophagus. As illustrated in Figure 23.13b, once food enters the pharynx, all routes except the desired one into the digestive tract are blocked off: of

—

Gastroesophageal ncter open

down

Longitudinal

the upper esophageal sphincter allows

contract, forcing

muscles

contract,

—

The tongue blocks off the mouth. The soft palate rises to close off the nasopharynx. The larynx rises so that the epiglottis covers its opening into the respiratory passageways, and the upper esophageal sphincter relaxes.

Food is squeezed through the pharynx and into the esophagus by wavelike peristaltic contractions (Figure 23.13c-e). Solid foods pass from the oropharynx to the stomach in 4 to 8 seconds; fluids pass in

(e)

to 2 seconds. Just before the peristaltic

1

food) reaches the

end

wave (and

of the esophagus, the gastro-

esophageal sphincter relaxes reflexively to allow food to enter the stomach.

^Ql^ homeostatic imbalance If

we

try to talk or inhale while swallowing, the var-

ious protective

mechanisms may be

short-circuited

and food may enter the respiratory passageways instead. This event typically triggers the cough reflex in an attempt to expel the food. •

The Stomach Below the esophagus, the GI tract expands to form the stomach (see Figure 23.1), a temporary "storage tank" where chemical breakdown of proteins begins

898

Maintenance of the Body

Unit IV

What

structural modification of a tunic underlies the

stomach's

FIGURE 23.14 section), (b)

Human

ability to

mechanically digest food?

Anatomy

Photograph of

of the stomach,

internal aspect of

(a)

Gross internal anatomy (frontal A Brief Atlas of the

stomach. (See

Body, Figure 53a.)

and food is converted to a creamy paste called chyme fkim "juice"). The stomach lies in the upper left quadrant of the peritoneal cavity, nearly hidden by the liver and diaphragm. Specifically it lies in the left hypochondriac, epigastric, and umbilical regions of the abdomen. Though relatively fixed at both ends, the stomach is quite movable in between. It tends to lie high and run horizontally in short, stout people (a steer-horn stomach) and is often elongated ;

vertically in

tall,

thin people

(a

J-shaped stomach).

Gross Anatomy The

adult stomach varies from 15 to 25

cm

(6 to

10

diameter and volume depend on An empty stomach has a volume of about 50 ml and a cross-sectional diameter only slightly larger than the large intestine, but when it is really distended it can hold about 4 L inches) long, but

how much

food

its

it

contains.

and may extend nearly all the way the stomach collapses inward, throwing its mucosa (and submucosal into (

1

gallon) of food

to the pelvis!

large, longitudinal folds called

wrinkle,

g

pooj

difi

uMop yeajq

Lp/UM

ui

s/je/rosnuj

sji

ui

ji

///eo/s/fyd jet^j s}uatua/\OLu

6u//wo//e '/(/anb//qo unj sjaqy aif)

apsniu i/jooius

p jaAej

pj/qj e seu_

}/

rugae

ruga

=

shown

in

(roo'ge;

fold).

The major Figure 23.14a.

regions of the stomach are

The small

("near the heart"),

cardiac region, or cardia

surrounds the cardiac

orifice

through which food enters the stomach from the esophagus. The fundus is its dome-shaped part, tucked beneath the diaphragm, that bulges superolaterally to the cardia. The body, the midportion of the stomach, is continuous inferiorly with the funnelshaped pyloric region. The wider and more superior part of the pyloric region, the pyloric antrum [antrum = cave) narrows to form the pyloric canal, which terminates at the pylorus. The pylorus is continuous with the duodenum (the first part of the small intestine) through the pyloric sphincter, which

stomach emptying [pylorus = gatekeeper). The convex lateral surface of the stomach is its greater curvature, and its concave medial surface is the lesser curvature. Extending from these curvatures are two mesenteries, called omenta controls

BuiujnijD iiqiuxd oi

When empty,

Chapter 23

(o-men'tah), that help tether the stomach to other digestive organs and the body wall (see Figure 23.30,

The

omentum

runs from the liver to the lesser curvature of the stomach, where it becomes continuous with the visceral peritoneum covering the stomach. The greater omentum drapes interiorly from the greater curvature of the stomach to cover the coils of the small intestine. It then runs dorsally and superiorly (enclosing the spleen on its way) to wrap the transverse portion of the large intestine before blending with the mesocolon, a dorsal mesentery that secures the large intestine to the p. 922).

lesser

peritoneum of the posterior abdominal wall. The greater omentum is riddled with fat deposits {oment = fatty skin) that give it the appearance of a parietal

lacy apron.

It

also contains large collections of

lymph nodes. The immune in

and macrophages these nodes "police" the peritoneal cavity and in-

The stomach

served by the autonomic nervous system. Sympathetic fibers from thoracic splanchnic nerves are relayed through the celiac is

plexus. Parasympathetic fibers are supplied by the

vagus nerve. The arterial supply of the stomach is provided by branches (gastric and splenic) of the celiac trunk (see Figure 19.22). The corresponding veins are part of the hepatic portal system (see Figure 19.27c) and ultimately drain into the hepatic portal vein.

899

antrum produce mucus and several hormones including most of the stimulatory hormone called gastrin. Glands of the stomach fundus and body, where most chemical digestion occurs, are the pyloric

substantially larger and produce the majority of the stomach secretions. The glands in these regions contain a variety of secretory cells, including the four

types described here: 1. Mucous neck cells, found in the upper, or "neck," regions of the glands, produce a different type of mucus from that secreted by the goblet cells

not yet understood what special function this acidic mucus performs. of the surface epithelium. It is

2.

Parietal cells, found mainly in the middle region

of the glands scattered

among

the chief cells (de-

scribed next), secrete hydrochloric acid (HCl) andin-

cells

traperitoneal organs.

The Digestive System

trinsic factor.

Although the

spherical

when viewed with

actually

have

prongs

three

parietal cells appear

a light microscope, they

that

exhibit

dense

microvilli (they look like fuzzy pitchforks!). This

structure provides a huge surface area for secreting

H+

and Cl into the stomach lumen. HCl makes the stomach contents extremely acidic (pH 1.5-3.5), a condition necessary for activation and optimal activity of pepsin, and harsh enough to kill many of the bacteria ingested with foods. The acidity also helps in food digestion by denaturing proteins and breaking

down cell walls

of plant foods. Intrinsic fac-

tor is a glycoprotein required for vitamin

B 12 absorp-

tion in the small intestine.

Microscopic Anatomy The stomach

3.

wall contains the four tunics typical of

most of the alimentary canal, but its muscularis and mucosa are modified for the special roles of the stomach. Besides the usual circular and longitudinal layers of smooth muscle, the muscularis externa has an innermost smooth muscle layer that runs obliquely (Figure 23.14a and Figure 23.15). This arrangement allows the stomach not only to move food along the tract, but also to churn, mix, and pummel the food, physically breaking it down into smaller fragments.

The

stomach mucosa is a simple columnar epithelium composed entirely of goblet cells, which produce a protective two -layer coat of alkaline mucus in which the surface layer lining epithelium of the

consists of viscous

mucus

that traps a layer of bicar-

it. This otherwise smooth dotted with millions of deep gastric pits

bonate-rich fluid beneath lining

is

(Figure 23.15), which lead into the gastric glands that produce the stomach secretion called gastric juice.

The

cells

forming the walls of the gastric

pits

composing the gastric glands vary in different stomach regions. For example, the cells in the glands of the cardia and pylorus are primarily mucus secreting, whereas cells of are primarily goblet cells, but those

Chief

cells

produce pepsinogen (pep-sin'o-jen),

the inactive form of the protein-digesting enzyme pepsin. The chief cells occur mainly in the basal regions of the gastric glands. When chief cells are stimulated, the first pepsinogen molecules they release

are activated by

HCl encountered

in the apical re-

gion of the gland (Figure 23.15c). But once pepsin is present, it also catalyzes the conversion of pepsinogen to pepsin. This positive feedback process is limited only by the amount of pepsinogen present. The activation process involves removal of a small peptide fragment from the pepsinogen molecule, causit to change shape and expose its active site. Chief cells also secrete insignificant amounts of lipases (fat-digesting enzymes).

ing

4.

Enteroendocrine

cells (en"ter-o-en'do-krin

endocrine") release a variety of

hormones

;

"gut

or hor-

monelike products directly into the lamina propria. These products, including gastrin, histamine, endorphins (natural opiates), serotonin, cholecystokinin, and somatostatin, diffuse into the blood capillaries, and ultimately influence several digestive system target organs (see Table 23.1, p. 905). Gastrin, in particular,

plays essential roles in regulating

stomach secretion and

mobility, as described shortly.

900

Maintenance of the Body

Unit IV

Gastric pits

Surface

r

epithelium

Q.

O 00 CD

(3

Mucous neck

Surface

cells

epithelium

Lamina

Mucosa

ac

propria

Parietal cell

ffl

D)

Muscularis

O

mucosae

u5 CO

Submucosa

O

(contains

Gastric

Oblique

submucosal

glands

layer

plexus)

Circular

Muscularis externa

-

layer

Longitudinal

(contains

layer

myenteric plexus)

Serosa Enteroendocrine

Stomach

wall

cell

(b)

(a)

FIGURE 23.15

Pepsinogen

Microscopic anatomy of the stomach.

(a)

Layers of stomach wall (longitudinal section).

(b)

Enlarged view of gastric

HCI-producing parietal

cells

pits, (c)

Locations of the

and the pepsin-secreting chief

Mitochondria in parietal

cells in

the gastric

pit.

Pepsin

HCI

cell

Parietal eel!

Chief cell

Entero-

endocrine cell

(c)

Chapter 23

The stomach mucosa

is

exposed to some of the

harshest conditions in the entire digestive tract. + Gastric juice is corrosively acidic (the H concentration in the stomach can be 100,000 times that found in blood), and its protein-digesting enzymes can digest the stomach itself. However, the stomach is not a passive victim of its formidable environment. It

mounts an

aggressive counterattack to protect

producing what

is

called the

mucosal

itself,

barrier.

Four

factors create this barrier: 1.

A thick coating of bicarbonate-rich mucus is built

up on the stomach

wall.

2. The epithelial cells of the mucosa are joined together by tight junctions that prevent gastric juice

from leaking into the underlying tissue 3.

Deep

in the gastric glands,

mucus is absent, plasma membranes of the alkaline

meable 4.

to

layers.

where the protective

the external faces of the glandular cells are imper-

HC1.

Damaged

epithelial

mucosal

shed and

cells are

quickly replaced by division of undifferentiated stem

where the gastric pits join the gastric glands. The stomach surface epithelium is completely renewed every three to six days. (However, cells that reside

glandular cells deep within the gastric glands have a

much

longer

life

The Digestive System

901

an enzyme that breaks down urea to C0 2 and ammonia (the ammonia then acts as a base to neutralize some of the stomach acid in their locale), (2) a cytotoxin that lesions the stomach epithelium, and (3) several proteins that act as chemotactic agents to attract macrophages and other defensive cells into the area. This bacterial-causal theory has been difficult to prove because the bacterium is found not only in some 70-90% of ulcer and gastritis sufferers but in more than 33% of healthy people as well. Even more troubling are studies that link this bacterium to some stomach cancers. The presence or absence of H. pylori is easily detected by a breath test. In ulcers colonized by it, the goal is to kill the embedded bacteria. A one- to two -week- long course of antibiotics (preferably two

complementary effects, such as metronidazole and tetracycline) in combination with a bismuth-containing compound, promotes healing and prevents recurrence. (Bismuth is the active inantibiotics with

H

gredient in Pepto-Bismol.) For active ulcers, a 2 receptor blocker, which inhibits HCl secretion by blocking histamine's effects, may also help. In non-

H 2 -receptor blocker drugs such as cimetidine (Tagamet) and ranitidine (Zantac) are the therapy of choice. • infectious cases,

span.)

Digestive Processes Occurring in the Stomach

HOMEOSTATIC IMBALANCE Anything that breaches the gel-like mucosal barrier causes inflammation of the stomach wall, a condi-

damage to the underpromote gastric ulcers, erosions of the stomach wall. The most distressing symptom of gastric ulcers is gnawing epigastric pain that seems tion called gastritis. Persistent lying tissues can

to bore through to your back. The pain typically occurs 1-3 hours after eating and is often relieved by

The danger posed by ulcers is perforastomach wall followed by peritonitis and,

Except for ingestion and defecation, the stomach is involved in the whole "menu" of digestive activities. Besides serving as a holding area for ingested food, the stomach continues the demolition job begun in the oral cavity by further degrading food both physically and chemically. It then delivers chyme, the product of its activity, into the small intestine. Protein digestion

is

initiated in the

stomach and

essentially the only type of enzymatic digestion

eating again.

is

tion of the

that occurs there. Dietary proteins are denatured by

perhaps, massive hemorrhage.

Common

predisposing factors for ulcer formation include hypersecretion of hydrochloric acid and hyposecretion of mucus. For years, the blame for causing ulcers was put on factors that favor high

HCl

or low

mucus production such

as aspirin

and

nonsteroidal anti-inflammatory drugs (ibuprofen),

smoking, alcohol, coffee, and stress. Although acid conditions are necessary for ulcer formation, acidity in and of itself is not sufficient to cause ulcer formation. Most recurrent ulcers (90%) are the work of acid-resistant, corkscrew- shaped Helicobacter pylori bacteria, which burrow beneath the mucus and destroy the protective areas.

help

mucosal

These bacteria

them do

layer,

leaving denuded

release several chemicals that

their "dirty

work" including

(

1

)

urease,

HCl produced by stomach glands in preparation for enzymatic digestion. The most important proteindigesting

enzyme produced by the

gastric

mucosa

is

pepsin. In infants, however, the stomach glands also secrete rennin,

an enzyme that

acts

on milk protein

converting it to a curdy substance that looks soured milk. Two common lipid-soluble substances alcohol and aspirin pass easily through the stomach mucosa into the blood, and may cause gastric bleeding; thus, these substances should be avoided by those with gastric ulcers. Despite the obvious benefits of preparing food to enter the intestine, the only stomach function essen(casein),

like

—

tial to life is

factor

is

secretion of intrinsic factor. Intrinsic

required for intestinal absorption of vitamin

B 12 needed ,

—

to

produce mature erythrocytes; in

its

902

Maintenance of the Body

Unit IV

Distension of the stomach

and duodenal

on stomach secretory

differing effects

have

walls

activity.

What

are these effects?

Stimulatory Events

Inhibitory Events

Cephalic phase

© and

©

1~

thought of food Stimulation

taste

Lack

Cerebral cortex

Sight

of -

and smell

Vagus

parasym-

nerve

pathetic

-

•

distension

Vagovagal

G

Medulla

acidity

declines

(
add

Glucose

Cytosol

Mitochondrial

Mitochondrion

cristae

q_f> Via

oxidative

phosphorylation •

\7

FIGURE 24.5

ATP

Sites of

formation during cellular

The Krebs

cycle

in

the

and the

each glucose molecule is broken down two molecules of pyruvic acid. The

to

membrane

nel protein called

pyruvic acid enters the mitochondrial

by coenzymes,

where the Krebs cycle decomposes it to C0 2 During glycolysis and the Krebs cycle, small amounts of ATP

electron transport chain, which

are

the mitochondria. During glycolysis,

across the

7

(through a

into the

.

electron transport chain reactions occur in

V

matrix,

respiration. Glycolysis occurs cytosol.

Via substrate-level phosphorylation

is

then transferred to the

membrane

is

of the cristae.

built

The

electron transport chain carries out

formed by substrate-level

oxidative phosphorylation, which

phosphorylation. Chemical energy from

accounts for most of the ATP generated

glycolysis and the Krebs cycle, in the form of energy-rich electrons picked up

by

membrane chan-

ATP synthase), some of this gradi-

take

cellular respiration.

and release. The

and anabolic pathways with glucose-6-phosphate.

catabolic

for carbohydrates all begin

ent energy is captured and used to attach phosphate groups to ADP.

Oxidation of Glucose

Carbohydrate Metabolism

Glucose is the pivotal fuel molecule in the oxidative (ATP-producing) pathways. Glucose is catabolized via the reaction

Because all food carbohydrates are eventually transformed to glucose, the story of carbohydrate metabolism is really a tale of glucose metabolism. Glucose enters the tissue cells by facilitated diffusion, a process that is greatly enhanced by insulin. Immediately upon entry into the cell, glucose is phosphorylated to glucose-6-phosphate by transfer of a phosphate group to its sixth carbon during a coupled reaction with ATP:

Glucose +

Most body

ATP

cells lack

this reaction, so

it

-> glucose- 6-PO4

+ ADP

the enzymes needed to reverse

effectively traps glucose inside the

Because glucose-6-phosphate is a different molfrom simple glucose, the reaction also keeps intracellular glucose levels low, maintaining a diffusion

cells.

ecule

gradient for glucose entry. cells,

kidney tubule

cells,

zymes needed to reverse tion, which reflects their

Only

and

intestinal

liver cells

mucosa

have the en-

this phosphorylation reac-

central roles in glucose up-

C 6 H 12 0 6 + 60 2 glucose

6H 2 0 + 6C0 2 +

oxygen

water

36

ATP +

heat

carbon dfoxide

This equation gives few hints that glucose breakdown is complex and involves three of the pathways included in Figures 24.3 and 24.5: 1.

Glycolysis

f

color-coded light orange through the

chapter) 2.

3.

The Krebs cycle (color-coded pale-green) The electron transport chain and oxidative phos-

pnorylation (color-coded violet)

These metabolic pathways occur in a definite and we will consider them sequentially.

A

order,

chemical steps by converted to two pyruvic acid molecules, glycolysis (gli-kol'i-sis; "sugar splitting") occurs in the cytosol of cells. All steps except the first,

Glycolysis

which glucose

is

series of ten

Chapter 24

Nutrition, Metabolism,

during which glucose entering the cell is phosphorylated to glucose- 6-phosphate, are fully reversible. Glycolysis is an anaerobic process (an-a'er-6b-ik; an = without, aero = air). Although this term is sometimes mistakenly interpreted to mean the path-

way occurs only interpretation

and Body Temperature Regulation

What would happen could not transfer

959

pathway if NADH + H' "picked up" hydrogens 10

in this

its

pyruvic acid?

in the absence of oxygen, the correct

that glycolysis does not use oxygen

is

and occurs whether or not oxygen is present. Figure 24.6 shows the three major phases of the glycolytic pathway. The complete glycolytic pathway appears in Appendix C. Sugar activation. In phase 1, glucose is phosphorand converted to fructose-6-phosphate, which is then phosphorylated again. These three steps yield fructose- 1,6-bisphosphate and use two ATP 1.

ylated

molecules.

The two

Key:

•

separate reactions of the sugar

= Carbon

atom

with ATP provide the activation energy needed to prime the later stages of the pathway hence phase 1 is sometimes called the energy investment phase. (The importance of activation energy is described in Chapter 2.)

—

2. Sugar cleavage. During phase 2, fructose- 1,6-bisphosphate is split into two 3-carbon fragments that exist (reversibly) as one of two isomers: glyceraldehyde (glis"er-al'de-hid) 3-phosphate or bishydroxyacetone (bis"hi-drok"se-as'e-ton) phosphate.

Oxidation and

ATP

formation. In phase 3, contwo major events happen. First, the two 3-carbon fragments are oxidized by the re+ moval of hydrogen, which is picked up by NAD Hence, some of glucose's energy is transferred to NAD + Second, inorganic phosphate groups (P;) are attached to each oxidized fragment by high-energy bonds. Later, as these terminal phosphates are cleaved off, enough energy is captured to form four ATP molecules. As noted earlier, formation of ATP 3.

sisting of six steps,

.

.

this

Phase 3 Sugar oxidation

and formation :

ATP

way is called substrate-level phosphorylation. The final products of glycolysis are two mole-

To Krebs x

cules of pyruvic acid and + +

two molecules of reduced with a net gain of two ATP molecules per glucose molecule. Four ATPs are produced, but remember that two are consumed in phase 1 to "prime the pump." Each pyruvic acid molecule has the formula C3H4O3, and glucose is C 6 H 12 0 6 Thus, between them the two pyruvic acid molecules have lost 4 hydrogen atoms, which are now bound to two molecules of NAD + Although a small amount of ATP has been harvested, the other two products of glucose oxidation (H 2 0 and C0 2 have yet to appear.

NAD (NADH

+

H

2 Lactic acid

cycle (aerobic

pathway)

),*

.

FIGURE 24.6

The three major phases of

glycolysis.

During phase 1, glucose is activated by phosphorylation and converted to fructose-1,6-bisphosphate. In phase 2, fructose1 ,6-bisphosphate is cleaved into two 3-carbon fragments (reversible isomers). In phase 3, the 3-carbon fragments are

ATP molecules are depends on whether or not

oxidized (by removal of hydrogen) and 4

.

formed. The fate of pyruvic acid molecular

02

is

available.

)

The most

which

fate of pyruvic acid,

of glucose's chemical energy,

still

contains

depends on the

H

-uoiiDunj 01 anuiiuoo

-ojp/fy dseajdj

*NAD

carries a positive charge +

hydrogen

pair,

NADH

+

H

is

+

(NAD thus, when it accepts the the resulting reduced product. )

II

\up\noo aiuAzud asepixo auj 'ua6

iueo pue peonpaj Apeai\e dje saiu/zuaoo aqj

uoiiepixo sjejjsqns

6uunp paAouudj

ai/}

|/e

ojuo p/ou louueo

;

duufaua asepixo auj asneoeq }/eu e oj aiuco p/no/v\

s/s/f|03/(|r)

960

Unit IV

Maintenance of the Body

oxygen at the time the pyruvic acid is + produced. Because the supply of NAD is limited, glycolysis can continue only if the reduced coen+ formed during glycolysis are zymes (NADH + H relieved of their extra hydrogen. Only then can they continue to act as hydrogen acceptors. When oxygen availability of

)

is

no problem. NADH + H + burden of hydrogen atoms to the enzymes

readily available, this

delivers its

is

of the electron transport chain in the mitochondria, to 0 2 forming water. However, not present in sufficient amounts, as + H+ might occur during strenuous exercise, unloads its hydrogen atoms back onto pyruvic acid, thus reducing it. This addition of two hydrogen

which

them

deliver

when oxygen

,

is

NADH

atoms

to pyruvic acid yields lactic acid (see

some

right of Figure 24.6), of the cells

gen

and

is

of

which

transported to the

bottom

diffuses out

liver.

When oxy-

again available, lactic acid is oxidized back to pyruvic acid and enters the aerobic pathways (the oxygen-requiring Krebs cycle and electron transport chain within the mitochondria), and is completely is

The liver may way back to glucose-

oxidized to water and carbon dioxide. also convert lactic acid

all

the

6-phosphate (reverse glycolysis) and then store glycogen or free it of its phosphate and release the blood if blood sugar levels are low.

Although

ATP

it

as

it

to

only 2 ATP molecules are produced per glucose molecule, as compared to the 36 ATP per glucose harvested when glucose is completely oxidized. Except for red blood cells (which typically carry out only glycolysis), prolonged anaerobic metabolism ultimately results in acid-base problems. Consequently, totally anaerobic conditions resulting in lactic acid formation provide only a temporary route for rapid ATP production. It can go on without tissue damage for the longest periods in skeletal muscle, for much shorter periods in cardiac muscle, and almost not at all in glycolysis generates

rapidly,

Krebs Cycle

Named

Krebs, the Krebs cycle

The Krebs

is

after its discoverer

Hans

the next stage of glucose

mitochonmatrix and is fueled largely by pyruvic acid produced during glycolysis and by fatty acids resulting from fat breakdown. After pyruvic acid enters the mitochondria, the cycle occurs in the

drial

first

(acetyl

CoA). Coenzyme

a sulfur-containing

tothenic acid, a

Acetyl

A (CoA-SH)

is

coenzyme derived from pan-

B vitamin.

CoA is now ready to

enter the Krebs cycle

and be broken down completely by mitochondrial enzymes. Coenzyme A shuttles the 2-carbon acetic acid to an enzyme that condenses it with a 4-carbon acid called oxaloacetic acid (ok"sah-lo"ah-set'ik) to

produce the 6-carbon citric acid. Because citric acid is the first substrate of the cycle, biochemists prefer to call the Krebs cycle the citric acid cycle. As the cycle moves through its eight successive steps, the

atoms

of citric acid are rearranged to pro-

duce different intermediate molecules, most called keto acids. The acetic acid that enters the cycle is broken apart carbon by carbon (decarboxylated) and oxidized, simultaneously generating + H+ and FADH 2 At the end of the cycle, acetic acid has been totally disposed of and oxaloacetic acid, the pickup molecule, is regenerated. Because two decarboxylations and four oxidations occur, the products of the Krebs cycle are two C0 2 molecules and four molecules of reduced coenzymes (3 + H+ and 1 FADH 2 ). The addition of water at certain steps accounts for some of the released hydrogen. One molecule of ATP is formed (via substrate-level phosphorylation) during each turn of the cycle. The detailed events of each of the eight steps of the Krebs

NADH

.

NADH

cycle are described in

Appendix C.

Now let's account for the pyruvic acid molecules entering the mitochondria. Each pyruvic acid yields three 2 molecules and five molecules of reduced coenzymes + + (equal to 1 FADH 2 and 4

C0

—

NADH

H

the removal of 10 hydrogen atoms). The products of glucose oxidation in the Krebs cycle are twice that (remember 1 glucose = 2 pyruvic acids): six 2

C0

,

ten molecules of reduced coenzymes, and two ATP molecules. Notice that it is these Krebs cycle reactions that produce the 2 evolved during glucose oxidation. The reduced coenzymes, which carry their extra electrons in high-energy linkages, must now be oxidized if the Krebs cycle and glycolysis are to continue. Although the glycolytic pathway is exclusive to carbohydrate oxidation, breakdown products of carbohydrates, fats, and proteins can feed into the Krebs cycle to be oxidized for energy. On the other hand, some Krebs cycle intermediates can be siphoned off to make fatty acids and nonessential amino acids. Thus the Krebs cycle, besides serving as the final common pathway for the oxidation of food fuels, is a source of building materials for anabolic reactions.

C0

the brain.

oxidation.

coenzyme A

order of business

is

to convert

it

to acetyl

CoA

via a three-step process (Figure 24.7): 1. Decarboxylation, in which one of pyruvic acid's carbons is removed and released as carbon dioxide gas. C0 2 diffuses out of the cells into the blood to be

expelled by the lungs.

Oxidation by the removal of hydrogen atoms, which are picked up by NAD + 2.

.

3. Combination of the resulting acetic acid with coenzyme A to produce the final product, acetyl

Electron Transport Chain and Oxidative Phosphorylation Like glycolysis, none of the reactions of the Krebs cycle use oxygen directly. This is the exclusive function of the electron transport

Chapter 24

Nutrition, Metabolism,

What two major kinds of chemical reactions occur and how are these reactions indicated

and Body Temperature Regulation

961

in

this cycle,

symbolically?

Cytosol

Mitochondrion (fluid matrix)

Citric acid

CoA

(initial

reactant)

NAD + Isocitric acid

Malic acid

Krebs cycle

a-Ketoglutaric acid

CoA NAD +

NADH+H + Key:

#

= Carbon atom Inorganic phosphate

= Coenzyme

CoA

A

FIGURE 24.7 Simplified version of the Krebs cycle. During each turn of the cycle, two carbon atoms are removed from the substrates as C0 2

atoms occur, producing four molecules + of reduced coenzymes (3 NADH + H and FADH 2 and one ATP is

the product of glycolysis, to acetyl CoA,

synthesized by substrate-level

pathway.

(decarboxylation reactions); four

phosphorylation.

oxidations by removal of hydrogen

decarboxylation and an oxidation

+

HQVN

*-

'uoiiepixo

+QVN

''6'9

'sbujAzubod

pue '^QD }° \saoiu9j

p

1

);

'+H uo\ionpai se umol/s

se u/woqs 'uoae/Axoqjeoag

An

additional

reaction occur to convert pyruvic acid,

the molecule that enters the Krebs cycle

962

Unit IV

Maintenance of the Body

Electron transport chain and oxidative

Glycolysis

>=ca>

phosphorylation

;7

Intermembrane space

Inner

mitochondrial

membrane

(carrying

@

from food)

Mitochondrial

FIGURE 24.8 Mechanism of oxidative phosphorylation. Schematic diagram showing the flow of electrons through the three major respiratory enzyme complexes (?) NADH dehydrogenase (FMN, Fe-S), cytochrome b-c 1( and cytochrome

—

©

©

oxidase (a-a 3

ATP Synthase

Electron Transport Chain

matrix

)

— of the electron transport

chain during the transfer of two electrons from reduced

oxygen. Coenzyme

NAD +

to

Q and cytochrome c

are mobile

and

act as carriers

gradient that drives them back across

the inner

The electron transport chain

is

an

membrane through the ATP ATP synthase uses

synthase complex. +

energy converter, transforming chemical + energy to the energy of a H gradient. As electrons flow along their energy gradient, some of the energy is used + by each complex to pump H from

the energy of H

the mitochondrial matrix into the

respiratory complex, less energy (2 ATP)

intermembrane space. These H

+

ions

to synthesize

flow (electrical energy)

ATP from ADP and

Oxidation of each

NAD +

yields 3 ATP.

unloads

is

NADH +

its

H

Because

+

FADH 2

H atoms beyond the

captured as

a result of

its

P,.

to

first

oxidation.

create an electrochemical proton

chain, which oversees the final catabolic reactions that occur on the mitochondrial cristae. However, be-

cause the reduced coenzymes produced in the Krebs cycle are the substrates for the electron transport chain, these pathways are coupled, and both phases are considered to be oxygen requiring (aerobic). In the electron transport chain, the hydrogens removed during the oxidation of food fuels are combined with 0 2 and the energy released during those reactions is harnessed to attach Pi groups to ADP. As noted earlier, this type of phosphorylation process is called oxidative phosphorylation. Let us peek under the hood of a cell's power plant and look more closely at this rather complicated process. ,

between

the complexes.

Most components

of

the

electron

transport

chain are proteins that are bound to metal atoms (cofactors).

These

proteins,

which form part

of the

mitochondrial cristae, vary in composition (Figure 24.8). For example, some of the proteins, the flavins, contain flavin mononucleotide (FMN) derived from the vitamin riboflavin, and others contain both sulfur (S) and iron (Fe). Most, however, are brightly colored iron-containing pigments called cytochromes (si'to-kromz; cyto = cell, chrom = color). Neighboring carriers are clustered together to form three major respiratory enzyme complexes that are alter-

up electrons the next complex in the

nately reduced and oxidized by picking

and passing them on

to

Chapter 24

The

Nutrition, Metabolism,

such complex accepts hydrogen 4 atoms from NADH + H', oxidizing it to NAD FADH 2 transfers its hydrogen atoms slightly farther along the chain. The hydrogen atoms delivered to the electron transport chain by the reduced coen+ zymes are quickly split into protons (H plus electrons. The electrons are shuttled along the crista membrane from one acceptor to the next. The protons escape into the watery matrix only to be picked up and deposited ("pumped") across the crista membrane into the intermembrane space by one of the three respiratory enzyme complexes. Ultimately the electron pairs are delivered to half a molecule of 0 2 (in other words, to an oxygen atom), creating oxygen + ions (O") that strongly attract H and form water as indicated by the reaction sequence.

and Body Temperature Regulation

963

first

.

)

2H + + Virtually

2e" +

H,0

V2O",

tion is formed during oxidative phosphorylation. Be+ H + and FADH 2 are oxidized as they cause release their burden of picked-up hydrogen atoms, the net reaction for the electron transport chain is

NADH

Coenzyme-2H + /i0 2 l

coenzyme +

reduced

oxidized

coenzyme

coenzyme

ATP

>

ATP

>

>

ATP ?

50

NADH+H

40

o 1

the water resulting from glucose oxida-

all

«>

TO

O

O o CD

>

CD i_

H 20

>
NADH + H > electron -> -» transport chain proton motive force ATP. Let's do a little bookkeeping to summarize the net energy gain from one glucose molecule. Once we have tallied the net gain of 4 ATP produced directly by substrate-level phosphorylations" (2 during glycolysis and 2 during the Krebs cycle), all that remains to be calculated is the number of ATP molecules produced by oxidative phosphorylation (Figure 24.1 1). Each NADH + H + that transfers a pair of highenergy electrons to the electron transport chain contributes enough energy to the proton gradient to generate between 2 and 3 ATP molecules. (We will round this yield off to 3 to simplify our calculations.) The oxidation of FADH 2 is less efficient because it doesn't donate electrons to the "top" of the electron + transport chain as does NADH + H but to a lower energy level. So, for each 2 H delivered by FADH 2 just 2 ATPs are produced (instead of 2+ or 3). Thus, + H + and the 2 FADH 2 produced the 8 during the Krebs cycle are "worth" 24 and 4 ATPs ent, cellular respiration is

the 686 kilocalories

The enzyme's subunits appear to work together like gears. As the ATP synthase core rotates, ADP and inorganic phosphate are pulled in and ATP is churned out, thus completing the process of oxidative phosphorylation. Studies of the molecular structure of ATP syn-

thase are providing an understanding of

works

(Figure 24.10).

of three

major

parts,

The enzyme complex

how

it

consists

each with several protein sub-

embedded in the crista membrane, knob extending into the mitochondrial matrix,

units: (1) a rotor (2)

a

The current crecauses the rotor and rod to rotate, just as flowing water turns a water wheel. This rotation activates catalytic sites in the knob where ADP and Pj are combined to make ATP. Notice something here. The ATP synthase works like an ion pump running in reverse. Recall from Chapter 3 that ion pumps use ATP as their energy source to transport ions against an electroand

(3)

a rod connecting the two. +

ated by the downhill flow of

H

chemical gradient. Here we have ATP synthases using the energy of a proton gradient to power ATP synthesis. The proton gradient also supplies energy to pump needed metabolites (ADP, pyruvic acid, inorganic phosphate) and calcium ions across the relatively

impermeable

membrane

is

stances, so

no "help"

crista

membrane. The outer

quite freely permeable to these subis

needed

there.

However, the

(kcal)

,

,

NADH

respectively.

The 2

NADH

+

H+

generated during

)

Chapter 24

Nutrition, Metabolism,

and Body Temperature Regulation

965

Cytosol

Glycolysis

Glucose

Electron transport chain and oxidative phosphorylation

|7_^>

•

(4

ATP-2 ATP

used

>/0 NADH

for

activation

2

energy)

Net +2

ATP

by substrate-level phosphorylation

FADH 2

- about 2 ATP

+2 ATP

+ about 34 ATP

used

for shuttling electrons

from

NADH

by substrate-level phosphorylation

by oxidative phosphorylation

produced

in

cytosol

+ H+ x 3 x 2

ATP

ATP

Maximum ATP yield per glucose

FIGURE

24.1

Energy yield during

1

glycolysis yields 4 (or 6)

ATP

cellular respiration.

molecules. Overall,

complete oxidation of 1 glucose molecule to C0 2 and H 2 0 yields 38 or 36 molecules of ATP (Figure 24. 1 1 ). The alternative figures represent the present un+ certainty about the energy yield of reduced NAD generated outside the mitochondria by glycolysis. The crista membrane is not permeable to reduced + H+ NAD + generated in the cytosol, so formed during glycolysis uses a shuttle molecule to

NADH

can store for

and then converted

As we know, shuttles cost money, and money used for this shuttle is ATP. At present,

as the

tachment

,

we have deducted

2

NAD + is probably the same as

ATP per electron pair. ATP to cover the "fare"

Thus, of the

and our bookkeeping comes 36 ATP per glucose as the possible energy yield. (Actually our

shuttle (Figure 24.11),

up with

a grand total of

maximum

figures are probably

tioned

earlier,

still

too high because, as

the proton motive force

is

men-

also used to

do other work.

Glycogenesis and Glycogenolysis Although most glucose is used to generate ATP molecules, unlimited amounts of glucose do not result in unlimited store large

ATP

synthesis, because cells cannot

amounts

of ATP.

When more

glucose

is

available than can be immediately oxidized, rising

ATP

concentrations eventually inhibit glucose catabolism and initiate processes that store glucose as either glycogen or fat. Because the body intracellular

account

to its isomer, glucose- 1 -phos-

The terminal phosphate group is cleaved enzyme glycogen synthase catalyzes the

the

that the net energy yield for reoxi-

fats

is "turned off" by high ATP levglucose molecules are combined in long chains to form glycogen, the animal carbohydrate storage product. This process, called glycogenesis [glyco = sugar; genesis = origin), begins when glucose entering cells is phosphorylated to glucose- 6 -phosphate

port chain.

is

than glycogen,

When glycolysis

phate.

dation of this reduced for FADH 2 that is, 2

fat

of stored energy.

els,

deliver its extra electron pair to the electron trans-

the consensus

much more

80-85%

off at-

growing glycogen chain (Figure 24.12). Liver and skeletal muscle cells are most active in glycogen synthesis and storage. When blood glucose levels drop, glycogen lysis (splitting) occurs. This process is known as of glucose to the

glycogenolysis (gli"ko-je-nol'i-sis). The enzyme glycogen phosphorylase oversees phosphorylation and cleavage of glycogen to release glucose- 1 -phosphate, which is then converted to glucoses-phosphate, a form that can enter the glycolytic pathway to be oxidized for energy. In muscle cells and most other cells, the glucose6-phosphate resulting from glycogenolysis is trapped because it cannot cross the cell membrane. However, hepatocytes (and some kidney and intestinal cells) contain glucose-6-phosphatase, an enzyme that removes the terminal phosphate, producing free glucose. Because glucose readily diffuses from the cell into the blood, the liver can use its glycogen stores to provide blood sugar for the benefit of other organs when blood glucose levels drop. Liver glycogen is

966

Maintenance of the Body

Unit IV

^Long-distance runners in particular are well aware of the practice of glycogen loading, popularly called "carbo loading," for endurance events. Glycogen loading "tricks" the muscles into storing more glycogen than they normally would. It involves (1) eating meals high in protein and fat while exercising

Blood glucose

Cell exterior

Hexokinase lucose-6-

(all

heavily over a period of several days (this depletes

tissue cells)

phosphatase

L-7

muscle glycogen

(present in liver kidney, and intestinal cells)

and then

two

(2)

to three

days before the event decreasing exercise intensity (to about 40% of the norm) and switching abruptly to a high-carbohydrate diet. This causes a rebound in muscle glycogen stores of two to four times the normal amount. However, glycogen retains water, and the resulting weight increase and fluid retention may hamper the ability of muscle cells to obtain adequate oxygen. Some athletes using the procedure

ADP

Glucose-6-phosphate

Mutase

Mutase

stores)

Glucose-1 -phosphate

have complained of cardiac and skeletal muscle pain. Consequently,

its

use

is

cautioned against.

Pyrophosphorylase

Gluconeogenesis

Glycogen phosphorylase

When

too little glucose is available to stoke the "metabolic furnace," glycerol and amino acids are converted to glucose. Gluconeogenesis, the process of forming new (neo) glucose from noncarbohydrate molecules, occurs in the liver. It takes place when dietary sources and glucose reserves have been depleted and blood glucose levels are beginning to drop. Gluconeogenesis protects the body, the nervous sys-

Uridine diphosphate

glucose Cell interior

w

Glycogen synthase

Key: Glycogenesis

Glycogen

tem

Glyco-

FIGURE 24.12 Glycogenesis and glycogenolysis. When glucose supplies exceed demands, glycogenesis,

the

conversion of glucose to glycogen for storage, occurs. Glycogenolysis, the breakdown of glycogen to release glucose,

is

stimulated by falling blood glucose levels. Notice

that glycogen

is

in particular,

from the damaging

effects of

blood sugar (hypoglycemia) by ensuring that synthesis can continue.

genosis

synthesized and degraded by different

enzymatic pathways.

Lipid

low

ATP

Metabolism

most concentrated source of enThey contain very little water, and the energy

Fats are the body's ergy.

from fat catabolism is approximately twice that from either glucose or protein catabolism 9 kcal

yield

per

gram

—

gram of carbohyMost products of fat digestion are lymph in the form of fatty-protein

of fat versus 4 kcal per

drate or protein. also

an important energy source

that have depleted their

A common

for skeletal

muscles

own

glycogen reserves. misconception is that athletes need to

amounts

improve their performance and maintain their muscle mass. Actually a diet rich in complex carbohydrates, which stores more muscle glycogen, is much more effective in sustaining intense muscle activity than are high-protein meals. Notice that the emphasis is on complex carbohydrates. Eating a candy bar before an athletic event to provide "quick" energy does more harm than good beeat large

of protein to

cause it stimulates insulin secretion, which favors glucose use and retards fat use at a time when fat use should be maximal. Building muscle protein or avoiding its loss requires not only extra protein, but also extra (protein-sparing) calories to meet the greater energy needs of the increasingly massive muscles.

transported in

droplets called chylomicrons (see Chapter 23). Eventually, the lipids in the chylomicrons are hydrolyzed by plasma enzymes, and the resulting fatty acids and glycerol are taken up by body cells and processed in

various ways.

Oxidation of Glycerol and Fatty Acids Of the various

only neutral fats are routinely oxidized for energy. Their catabolism involves the separate oxidation of their two different building lipids,

blocks: glycerol

and

fatty acid chains.

Most body

cells easily convert glycerol to glyceraldehyde phos-

phate, a glycolysis intermediate that enters the Krebs cycle. Glyceraldehyde is equal to half a glucose

molecule, and

ATP

energy harvest from

its

complete

Chapter 24

oxidation

is

Nutrition, Metabolism,

and Body Temperature Regulation

967

approximately half that of glucose

(18 ATP/glycerol).

Beta oxidation, the

initial

phase of fatty acid

oxidation, occurs in the mitochondria. oxidation, dehydration, volved, the net result

is

Although

and other reactions are

in-

that the fatty acid chains are

broken apart into two-carbon acetic acid fragments, and coenzymes are reduced (Figure 24.13). Each acetic acid molecule is fused to coenzyme A, forming acetyl

CoA. The term "beta oxidation"

reflects the

fact that the carbon in the beta (third) position is oxidized during the process and cleavage of the fatty

between the alpha and beta carbons. Acetyl CoA is then picked up by oxaloacetic acid and enters the aerobic pathways to be oxidized to C0 2 and H 2 0. Notice that unlike glycerol, which enters the glycolytic pathway, acetyl CoA resulting from fatty acid breakdown cannot be used for gluconeogenesis because the metabolic pathway is irreversible past

Coenzyme A Glyceraldehyde phosphate

acid in each case occurs

r

NAD +

NADH P Oxidation in the mito-

Glycolysis

+ H+

FAD

chondria Pyruvic acid

Cleavage

pyruvic acid.

enzyme snips

Lipogenesis and Lipolysis

off

2C fragments

There is a continuous turnover of neutral fats in adipose tissue. New fats are "put in the larder" for later use, while stored fats are broken down and released to the blood. That bulge of fatty tissue you see today does not contain the same fat molecules it did a

month

ago.

Glycerol and fatty acids from dietary fats not immediately needed for energy are recombined into triglycerides and stored. About 50% ends up in subcutaneous tissue; the balance is stockpiled in other fat depots of the body. Triglyceride synthesis, or lipogenesis (Figure 24.14), occurs when cellular ATP and glucose levels are high. Excess ATP also leads to an accumulation of acetyl CoA and glyceraldehydeP0 4 two intermediates of glucose metabolism that would otherwise feed into the Krebs cycle. But when these two metabolites are present in excess, they are channeled into triglyceride synthesis pathways. Acetyl CoA molecules are condensed together, forming fatty acid chains that grow two carbons at a time. (This accounts for the fact that almost all fatty acids in the body contain an even number of carbon atoms.) Because acetyl CoA, an intermediate in glucose catabolism, is also the starting point for fatty acid synthesis glucose is easily converted to fat. Glyceraldehyde-P0 4 is converted to glycerol, which is condensed with fatty acids to form triglycerides. Thus, even if the diet is fat-poor, carbohydrate intake can provide all the raw materials needed to form neutral fats. When blood sugar is high, lipogenesis is the major activity in adipose tissues and is also an important liver function. ,

Lipolysis (ll-pol'i-sis; "fat splitting"), the breakdown of stored fats into glycerol and fatty acids, is

FIGURE

24.1 3

glycerol portion

Initial is

phase of

lipid

oxidation. The

converted to glyceraldehyde phosphate, and completes the glycolytic

a

glycolysis intermediate,

pathway through pyruvic acid to acetyl CoA. The fatty acids undergo beta oxidation. In this process the fatty acids are first activated by a coupled reaction with ATP and combined with

coenzyme A. After being oxidized twice (reducing and FAD), the acetyl CoA created in (3 oxidation

NAD +

cleaved

off

is

and the process begins again.

essentially lipogenesis in reverse.

The

fatty acids

and

glycerol are released to the blood, helping to ensure

that body organs have continuous access to fat fuels

(The liver, cardiac muscle, and resting skeletal muscles actually prefer fatty acids as an energy fuel.) The meaning of the adage "fats burn in the flame of carbohydrates" becomes

for aerobic respiration.

clear

when carbohydrate

intake

is

inadequate.

Under

such conditions, lipolysis is accelerated as the body attempts to fill the fuel gap with fats. However, the ability of acetyl CoA to enter the Krebs cycle depends

on the

availability of oxaloacetic acid to act as the

pickup molecule. oxaloacetic acid

When

is

carbohydrates are deficient, converted to glucose (to fuel the

>

968

Unit IV

What

is

Maintenance of the Body

the central molecule

in lipid

metabolism?

Stored fats in adipose tissue

1

Neutral fats (triglycerides)

= Anabolic (lipogenesis

When

FIGURE 24.14 Metabolism of When needed for

triglycerides.

energy, dietary or stored fats enter the catabolic pathways. Glycerol enters the glycolytic

pathway

(as

glyceraldehyde

be synthesized and stored in fat depots, the intermediates are drawn from glycolysis and the Krebs cycle in a reversal of the processes noted above.

source, the

(lipogenesis)

breakdown products (fatty acids — acetyl CoA) in the form of ketone bodies. Excessive amounts of carbohydrates and amino acids are

Likewise, excess dietary fats are stored

converted to triglycerides (lipogenesis).

phosphate) and the fatty acids are broken down by beta oxidation to acetyl

in

CoA, which enters the Krebs

are

brain).

cycle.

Without oxaloacetic

fats are to

adipose in

tissues.

from

fat

acid, fat oxidation is

metabolism are quite

different

and

should not be confused.)

HOMEOSTATIC IMBALANCE When

ketone bodies accumulate in the blood, ketoand large amounts of ketone bodies are excreted in the urine. Ketosis is a common conse-

sis results

quence

of

starvation,

unwise dieting

releases their

also

triglycerides

excess or are the primary energy

incomplete, acetyl CoA accumulates, and via a process called ketogenesis, the liver converts acetyl CoA molecules to ketones, or ketone bodies, which are released into the blood. Ketone bodies include acetoacetic acid, p-hydroxybutyric acid, and acetone, all formed from acetic acid. (The keto acids cycling through the Krebs cycle and the ketone bodies resulting

When

liver

(in

which

inadequate amounts of carbohydrates are eaten), and diabetes mellitus. Because most ketone bodies are organic acids, the outcome of ketosis is metabolic acidosis. The body's buffer systems cannot tie up the acids (ketones) fast enough, &nd blood pH drops to dangerously low levels. The person's breath smells fruity as acetone vaporizes from the lungs, and breathing becomes more rapid as the respiratory system tries to reduce blood carbonic acid by blowing off C0 2 to force the blood pH up. In severe untreated cases, the person may become comatose or even die as the acid pH depresses the nervous system. •

Synthesis of Structural Materials body

use phospholipids and cholesterol to build their membranes. Phospholipids are also important components of myelin sheaths of neurons.

All

cells

In addition, the liver 1 synthesizes lipoproteins for transport of cholesterol, fats, and other substances in the blood; (2) makes the clotting factor called tissue factor; (3) synthesizes cholesterol from acetyl (

)

Chapter 24

CoA; and

Nutrition, Metabolism,

and Body Temperature Regulation

969

uses cholesterol to form bile salts. The and adrenal cortex use cholesterol to

(4)

ovaries, testes,

synthesize their steroid hormones.

Protein Metabolism Like

all

limited

other biological molecules, proteins have a life

span and must be broken down and

replaced before they begin to deteriorate. Newly ingested amino acids transported in the blood are

taken up by cells by active transport processes and used to replace tissue proteins at the rate of about 100 grams each day. When more protein is ingested than is needed for these anabolic purposes, amino acids are oxidized for energy or converted to fat.

Oxidation of Amino Acids amino

acids can be oxidized for energy, they deaminated, that is, their amine group must be (NH 2 must be removed. The resulting molecule is then converted to pyruvic acid or to one of the keto acid intermediates in the Krebs cycle. The key mole-

Before

)

cule in these conversions

is

the nonessential

acid glutamic acid (gloo-tam'ik).

The

amino

events that oc-

cur (Figure 24.15) are: 1.

Transamination (trans"am-i-na'shun). A numamino acids can transfer their amine group to

ber of

Excreted

Krebs cycle keto acid), thereby transforming a-ketoglutaric acid to glutamic acid. In

a-ketoglutaric acid

(a

in

urine

Oxidative deamination. In the liver, the amine group of glutamic acid is removed as ammonia

FIGURE 24.15 Transamination and oxidative processes that occur when amino acids are oxidized for energy. Transamination involves the switching of an amine group from an amino acid to a keto acid, usually a-ketoglutaric acid. As a result the original amino acid becomes a keto acid, and the keto acid becomes an amino

(NH 3 ), and

acid, typically glutamic acid. In oxidative

amino acid becomes a keto has an oxygen atom where the amine

the process, the original acid (that

is, it

group formerly was). This reaction

is fully

reversible.

2.

a-ketoglutaric acid

is

regenerated.

NH 3

The

molecules are combined with C0 2 yielding urea and water. The urea is released to the blood and removed from the body in urine. Because ammonia is toxic to body cells, the ease with which glutamic acid funnels amine groups into the urea cycle is extremely important. This mechanism rids the body not only of 3 produced during oxidative deamination, but also of bloodborne 3 produced liberated

,

NH

NH

by intestinal

bacteria.

Keto acid modification. The goal of amino acid degradation is to produce molecules that can be either oxidized in the Krebs cycle or converted to glucose. Hence, keto acids resulting from transamination are altered as necessary to produce metabolites that can enter the Krebs cycle. The most important of these metabolites are pyruvic acid, acetyl 3.

CoA, a-ketoglutaric

acid,

and oxaloacetic acid

(Fig-

ure 24.7). Because the reactions of glycolysis are redeaminated amino acids that are converted to pyruvic acid can be reconverted to glucose and contribute to gluconeogenesis.

versible,

amine group of glutamic acid then combined with

C0 2

is

by the

deamination the

released as liver cells

ammonia and

to form urea.

Protein Synthesis

Amino

most important anabolic nutrients. Not only do they form all protein structures, but they form the bulk of the body's functional molecules as well. As described in Chapter 3, protein synthesis occurs on ribosomes, where cytoplasmic enzymes oversee the formation of peptide bonds linking the amino acids together into protein polymers. The amount and type of protein synthesized are precisely controlled by hormones (growth hormone, thyroxine, sex hormones, and others), and so protein anabolism reflects the hormonal balance at acids are the

each stage of life. During your lifetime, your cells will have synthesized 225-450 kg (about 500-1000 pounds) of proteins, depending on your size. However, you do not need to consume anywhere near that amount of

— 970

Maintenance of the Body

Unit IV

TARI F ?A A s

Thumhn^i IIIUIMUIIuM ^urnmarv JUIIIIIIdly

nf IvIClaUwMV. Mptahn ir IXCavLIUIIj Rpar+innc Ul

— r r + nc oarDonyardres

f

i

La

L-,

.

/

/-J

-i

Cellular respiration

Reactions that together complete the oxidation of glucose, yielding CO2, H2O, and

Glycolysis

Conversion of glucose to pyruvic acid

oncogenesis

roiyrner iZdiion ot giucose 10 Torm yiycoyen

oiycogenoiysis

nyaroiysis ot yiycoyen to yiucose

oiuconeoyenesis

rorrnaTion ot yiucose Trom noncaroonyaraie precursors

Krebs cycle

Complete breakdown

ATP

monomers

ot pyruvic acid to

C0 2

,

yielding small

amounts

ot

ATP and reduced

CUtrNZynifcrb

Electron transport chain

H removed during oxidations to H~ and P„ forming ATP

Energy-yielding reactions that

split

proton gradient used to bond

ADP to

e~~

and create

a

LlplQS

Beta oxidation

Conversion of

Lipolysis

DreaKaown

Lipogenesis

Formation of

fatty acids to acetyl

ot npias 10 Taiiy acias lipids

from acetyl

CoA ana

glycerol

CoA and

glyceraldehyde phosphate

Proteins Transfer of an

Transamination

amine group from an amino acid to

ot-ketoglutaric acid, thereby transforming

a-ketoglutaric acid to glutamic acid

Removal of an amine group from glutamic acid as ammonia and regenerating a-ketoglutaric (NH 3 is converted to urea by the liver)

Oxidative deamination

acid

protein because nonessential

amino

acids are easily

formed by siphoning keto acids from the Krebs cycle and transferring amine groups to them. Most of these transformations occur in the liver, which provides

nearly

all

the

nonessential

amino

acids

needed to produce the relatively small amount of protein that the body synthesizes each day. However, a complete set of amino acids must be present for protein synthesis to take place, so all essential

amino

acids

must be provided by the

diet. If

are not, the rest are oxidized for energy even

some

though

they may be needed for anabolism. In such cases, negative nitrogen balance results because body protein is broken down to supply the essential amino acids needed. The various metabolic reactions described thus far are

summarized

briefly in Table 24.4.

Catabolic-Anabolic Steady State of the Body The body exists

in a

dynamic

catabolic -anabolic state

as organic molecules are continuously broken

and

— frequently

down

at a head-spinning rate. The blood is the transport pool for all body cells, and it contains many kinds of energy sources glucose, ketone bodies, fatty acids, glycerol, and lactic acid. Some organs routinely use blood energy sources other than glucose, thus saving glucose for

rebuilt

tissues with stricter glucose requirements (see Table

24.5 on

p. 975).

— amino carbohy— can be drawn on to meet

The body nutrient pools drate,

and

fat stores

acid,

its

varying needs (Figure 24.16). These pools are interconvertible because their pathways are linked by key intermediates (see Figure 24.17). The liver, adipose tissue, and skeletal muscles are the primary effector organs determining the amounts and direction of the conversions shown in the figure. The amino acid pool is the body's total supply of free amino acids. Small amounts of animo acids and proteins are lost daily in : urine and in sloughed hairs and skin cells. Typically these lost molecules are replaced via the diet; otherwise, amino acids arising from tissue breakdown return to the pool. This pool is the source of amino acids used for protein synthesis and in the formation of amino acid derivatives. In addition, as described above, deaminated amino acids can participate in gluconeogenesis. Not all events of amino acid metabolism occur in all cells. For example, only the liver forms urea. Nonetheless, the concept of a common amino acid pool is valid because all cells are connected by the blood.

Because carbohydrates are easily and frequently converted to fats, the carbohydrate and fat pools

There pool and

are usually considered together [Figure 24.17).

are

the

two major differences between this acid pool: 1 Fats and carbohydrates are

amino

(

)

Chapter 24

Nutrition, Metabolism,

and Body Temperature Regulation

971

Food Intake

Dietary proteins

Dietary carbohydrates

and amino acids

and

lipids

Pool of carbohydrates and fats (carbohydrates ^ fats)

7 Components of structural and

Nitrogen-containing derivatives

hormones,

functional

(e.g.,

proteins

neurotransmitters)

Some

FIGURE 24.16

Specialized derivatives

Catabolized

(e.g., steroids, acetylcholine);

for

in

urine

Some

lost via

co 2

surface

secretion, cell sloughing

Storage forms

excreted via lungs

Carbohydrate/fat and amino acid pools.

oxidized directly to produce cellular energy, whereas

amino

energy

bile salts

etc.)

Excreted

lost via cell

sloughing, hair loss

components (membranes,

Structural of cells

Absorptive and Postabsorptive States

acids can be used to supply energy only after

Metabolic controls act to equalize blood concentrations of energy sources between two nutritional

being converted to a carbohydrate intermediate (a keto acid). (2) Excess carbohydrate and fat can be stored as such, whereas excess amino acids are not stored as protein. Instead, they are oxidized for energy or converted to fat or glycogen for storage.

states.

Sometimes

referred to as the fed state, the

absorptive state is the time during and shortly after when nutrients are flushing into the blood

eating,

Carbohydrates Proteins

Neutral fats (triglycerides)

Glycogen

H H H H

Glucose

Glucose-6-phosphate

"*

Glyceraldehyde phosphate *-

Lactic acid

Pyruvic acid

4

Excreted

in

urine

FIGURE 24.17

Interconversion of carbohydrates, fats, and proteins. The adipose tissue, and skeletal muscles are the primary effector organs determining the amounts and direction of the conversions shown. liver,

'

972

Maintenance of the Body

Unit IV

Major energy

Major metabolic thrust: anabolism and energy storage

Liver metabolism: amino

fuel:

acids deaminated and used for energy or stored as fat

glucose (dietary)

Amino

Glucose

Amino

Glycerol and

1

acids

fatty

1

acids

acids

Glucose Keto acids (in liver

f

\

Proteins

'*7

C02 + H 2 0

Triglycerides

+

1 Glycogen

:

ATP

C0 2

\S

+

H„0

|

ijor

events of the absorptive state muscle: Glycogen

In

In all tissues:

Glucose

C0 2

+ H 20

Protein

Amino acids

Glucose

Fats

—

In

In liver:

adipose

tissue:

Glycogen

Keto acids

\


efferent arterioles —> peritubular capillary beds -* interlobular veins -* arcuate veins -» interlobar veins -> renal vein. 5.

1006-1022)

(pp.

Step

A renal capsule,

Internal

Kidney Physiology: Mechanisms of Urine Formation

The more numerous

cortical

nephrons are located

al-

most entirely in the cortex; only a small part of their loop of Henle penetrates into the medulla. Juxtamedullary nephrons are located at the cortex-medulla junction, and their loop of Henle dips deeply into the medulla. Instead of forming peritubular capillaries, the efferent arterioles of many of the juxtamedullary nephrons form unique bundles of straight vessels, called vasa recta, that serve tubule segments in the medulla. Juxtamedullary nephrons and the vasa recta play an important role in establishing the medullary osmotic gradient. directly

10. Collecting ducts receive urine from many nephrons and help concentrate urine. They form the medullary pyramids.

The

Filtration, pages

1-15.

The

renin-angiotensin mechanism mediated by the JG systemic blood pressure via generation of angiotensin II, which promotes aldosterone secretion. 8.

cells raises

Step

2:

Tubular Reabsorption

(pp.

1010-1014)

During tubular reabsorption, needed substances are rethe filtrate by the tubule cells and returned to the peritubular capillary blood. The primary active transport + + + of Na by a Na -K ATPase pump at the basolateral mem+ brane accounts for Na reabsorption and establishes the 9.

moved from

electrochemical gradient that drives the reabsorption of + most other solutes and H 2 0. Na enters at the luminal surface of the tubule cell via facilitated diffusion through channels or as part of a cotransport mechanism. is driven by electrochemiby active reabsorption of sodium ions. Water, many anions, and various other substances (for example, urea) are reabsorbed passively by diffusion via transcellular or paracellular pathways.

10. Passive tubular reabsorption

cal gradients established

juxtaglomerular apparatus is at the point of contact arteriole and the first part of the distal convoluted tubule. It consists of the juxtaglomerular (JG) cells and the macula densa.

1 1 Secondary active tubular reabsorption occurs by co+ transport with Na via protein carriers. Transport of such substances is limited by the number of carriers available. Substances reabsorbed actively include nutrients and some

BTB

ions.

1 1

.

between the afferent

12.

Urinary System; Topic: Anatomy Review, pages 1-20.

The

filtration

membrane

.

12. Certain substances (creatinine, drug metabolites, etc.)

consists of the fenestrated

glomerular endothelium, the intervening basement membrane, and the podocyte-containing visceral membrane of the glomerular capsule. It permits free passage of substances smaller than (most) plasma proteins.

are not reabsorbed or are reabsorbed incompletely because of

the lack of carriers, their 13. tion.

size,

or nonlipid solubility.

The proximal tubule cells are most active in reabsorpMost of the nutrients, 65% of the water and sodium

Chapter 25 and the bulk of actively transported ions are reabsorbed in the proximal convoluted tubules. ions,

sodium ions and water octubules and collecting ducts and is hor-

14. Reabsorption of additional

curs in the distal monally controlled. Aldosterone increases the reabsorption

sodium (and obligatory water reabsorption); antidiuretic hormone enhances water reabsorption by the collecting of

4.

The Urinary System

Daily urinary volume

is

typically 1.5-1.8 L, but this

depends on the state of hydration

Ureters

(p.

1031

of the body.

1023)

1. The ureters are slender tubes running retroperitoneally from each kidney to the bladder. They conduct urine by peristalsis from the renal pelvis to the urinary bladder.

ducts.

Urinary Bladder Step 3: Tubular Secretion 15. Tubular secretion

is

a

(p.

means

of adding substances to the

(from the blood or tubule cells). It is an active process important in eliminating drugs, urea, and excess ions and in maintaining the acid-base balance of the blood. filtrate

that

is

Regulation of Urine Concentration and Volume (pp.

1014-1018)

16.

The graduated hyperosmolality of due to the cycling of NaCl and

(largely

is

dilute

medullary interstitium. The filtrate and medullary fluid at the tip of the loop of Henle are hyperosmolar. The thick ascending limb is impermeable to water, + but Na and CP are actively transported out of the fil-

The

filtrate

Na

becomes and CP

+

more

dilute as

move

passively out of the thin portion of the ascending

continues to lose

salt.

limb.

As

flows through the collecting ducts in the inner medulla, urea diffuses into the interstitial space. Some urea enters the ascending limb and is recycled. The blood flow in the vasa recta is sluggish, and the contained blood equilibrates with the medullary interstitial fluid. Hence, blood entering and exiting the medulla in the vasa recta is isotonic to blood plasma and the high solute concentration of the medulla is

17. In the absence of antidiuretic

formed because the is

hormone,

adventitia.

Urethra

simply allowed to pass from the kidneys.

As blood levels of antidiuretic hormone rise, the collectbecome more permeable to water, and water moves out of the filtrate as it flows through the hyperosmotic medullary areas. Consequently, more concentrated urine is produced, and in smaller amounts. 18.

2. Where the urethra leaves the bladder, it is surrounded by an internal urethral sphincter, an involuntary smooth muscle sphincter. Where it passes through the urogenital diaphragm, the voluntary external urethral sphincter is formed by skeletal muscle.

3. In

females the urethra

males and semen.

urine. In

Micturition 1.

Micturition

Urinary System; Topics: Early Filtrate Processing, pages 1-22; Late Filtrate Processing, pages 1-13. (pp.

19. Renal clearance

which the kidneys

is

1018-1022)

the

volume flow rate (ml/min) at plasma of a particular solute.

clear the

Studies of renal clearance provide information about renal function or the course of renal disease.

Urine

(p.

Urine

is

1022) typically clear, yellow, aromatic,

acidic. Its specific gravity ranges

Urine

from 1.001

and

slightly

to 1.035.

95% water;

solutes include nitrogenous wastes and creatinine) and various ions (always sodium, potassium, sulfate, and phosphate). 2.

is

(urea, uric acid,

3.

it is

(pp. is

20

3-4 cm long and conducts only long and conducts both urine

is

cm

1025-1027)

emptying

of the bladder.

Stretching of the bladder wall by accumulating urine initiates the micturition reflex, in which parasympathetic fibers, in response to signals from the micturition center of the pons, cause the detrusor muscle to contract and the internal urethral sphincter to relax (open). 2.

Because the external sphincter is voluntarily controlled, micturition can usually be delayed temporarily.

3.

Developmental Aspects of the Urinary System (pp. 1027-1029) 1

.

Three

mesonephric, and metamesoderm. The metaexcreting urine by the third month of development.

sets of kidneys (pronephric,

nephric) develop from the intermediate

nephros 2.

is

Common congenital

abnormalities are horseshoe kidney,

polycystic kidney, and hypospadias.

Renal Clearance

.

1025)

1. The urethra is a muscular tube that conveys urine from the bladder to the body exterior.

The kidneys

of newborns cannot concentrate urine,- their small and voiding is frequent. Neuromuscular maturation generally allows toilet training for micturition to begin by 1 8 months of age. 3.

bladder

1

(p.

dilute urine is

dilute filtrate reaching the collecting

ing ducts

WJI

its outlet.

The

filtrate

maintained.

duct

rounds

urea) ensures that

mOsm

trate into the interstitial space.

that outline the trigone. In males, the prostate gland sur-

bladder wall consists of a transitional epitheliumcontaining mucosa, a three-layered detrusor muscle, and an

(hypo-osmolar). This allows urine with osmolalities ranging to 1200 to be formed. The descending limb of the loop of Henle is permeable to water, which leaves the filtrate and enters the

it

1023-1024)

1. The urinary bladder, which functions to store urine, is a distensible muscular sac that lies posterior to the pubic symphysis. It has two inlets (ureters) and one outlet (urethra)

2.

the medullary fluids

the filtrate reaching the distal convoluted tubule

from 65

(pp.

1014)

Substances not normally found in urine include glucose, and bile pigments.

proteins, erythrocytes, pus, hemoglobin,

is

The most common urinary system problems in children and young to middle-aged adults are bacterial infections.

4.

5. Renal failure is uncommon but serious. The kidneys are unable to concentrate urine, nitrogenous wastes accumulate in the blood, and acid-base and electrolyte imbalances occur.

With age, nephrons are lost, the filtration rate decreases, and tubule cells become less efficient at concentrating urine. 6.

7. Bladder capacity and tone decrease with age, leading to frequent micturition and (often) incontinence. Urinary retention is a common problem of elderly men.

1032

Maintenance of the Body

Unit IV

Review Questions Multiple Choice/Matching

16. Explain the process

(Some questions have more than one correct answer. Select the best answer or answers from the choices given.)

of urine?

The lowest blood concentration of nitrogenous waste 1 occurs in the (a) hepatic vein, (b) inferior vena cava, (c) renal .

artery, (d) renal vein. 2. The glomerular capillaries differ from other capillary networks in the body because they (a) have a larger area of anastomosis, (b) are derived from and drain into arterioles, (c) are not made of endothelium, (d) are sites of filtrate

formation. 3.

How does

17.

and purpose

of tubular secretion.

aldosterone modify the chemical composition

18. Explain why the filtrate becomes hypotonic as it flows through the ascending limb of the loop of Henle. Also explain why the filtrate at the tip of the loop of Henle (and the interstitial fluid of the deep portions of the medulla) is

hypertonic.

How does urinary bladder anatomy support its

19.

storage

function? 20. Define micturition and describe the micturition reflex.

Damage

medulla would interfere

to the renal

the functioning of the

convoluted tubules,

first

with

glomerular capsules, (b) distal collecting ducts, (d) proximal convo-

(a)

(c)

21. Describe the changes that occur in kidney and bladder in old age.

anatomy and physiology

luted tubules. 4.

Which

cells? (a)

Critical is

Na

+ ,

reabsorbed by the proximal convoluted tubule + (b) K (c) amino acids, (d) all of the above.

Thinking and

Clinical Application

,

Glucose is not normally found in the urine because it (a) does not pass through the walls of the glomerulus, (b) is kept in the blood by colloid osmotic pressure, (c) is reabsorbed by the tubule cells, (d) is removed by the body cells

Questions

5.

before the blood reaches the kidney.

protein-restricted diet

glomerulus is directly related to (a) water reabsorption, (b) arterial blood pressure, (c) capsular 6. Filtration at the

hydrostatic pressure,

(d)

acidity of the urine.

Renal reabsorption (a) of glucose and many other substances is a T m -limited active transport process, (b) of + chloride is always linked to the passive transport of Na (c) is the movement of substances from the blood into the nephron, (d) of sodium occurs only in the proximal tubule. 7.

,

voided urine sample contains excessive urochrome, it has (a) an ammonia-like odor, (b) a pH below normal, (c) a dark yellow color, (d) a pH above normal. 8. If a freshly

amounts

of

9. Conditions such as diabetes mellitus, starvation, and low-carbohydrate diets are closely linked to (a) ketosis, (b) pyuria, (c) albuminuria, (d) hematuria.

What

1 1 Trace the pathway a creatinine molecule takes from a glomerulus to the urethra. Name every microscopic or gross structure it passes through on its journey.

diuretics are prescribed to

manage

2.

While repairing

a frayed utility wire, Herbert,

an

experi-

enced lineman, slips and falls to the ground. Medical examination reveals a fracture of his lower spine and transection

lumbar region of the spinal cord. How will Herbert's micturition be controlled from this point on? Will he ever again feel the need to void? Will there be dribbling of urine between voidings? Explain the reasoning behind all your responses. of the

What

is cystitis?

sufferers

than men?

3.

4. Hattie,

regions

the importance of the adipose capsule that surrounds the kidney? is

and

her ascites (accumulated fluid in the peritoneal cavity). How will diuretics reduce this excess fluid? Name and describe the mechanism of action of two types of diuretics. Why is her diet salt-restricted?

radiates

Short Answer Essay Questions 10.

1. Mrs. Bigda, a 60-year-old woman, was brought to the hospital by the police after falling to the pavement. She is found to have alcoholic hepatitis. She is put on a salt- and

aged 55,

from her

Why are women more frequent cystitis is

awakened by excruciating pain that abdomen to the loin and groin

right

on the same

side.

The pain

is

not continuous but

recurs at intervals of 3 to 4 minutes. Diagnose her problem,

and

cite factors that

explain

why

might favor

Hattie's pain

comes

its

occurrence. Also,

in "waves."

.

12. Explain the important differences

and renal

filtrate,

of the filtration

and

mechanisms

woman's

risk for

between blood plasma

relate the differences to the structure

membrane.

13. Describe the

5. Why does use of a spermicide increase a urinary tract infection?

that contribute to renal

MyA&F

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autoregulation. 14. Describe

what

is

involved in active and passive tubular

reabsorption. 15. Explain

how

the peritubular capillaries are adapted for

receiving reabsorbed substances.

www.mariebmap.com. Navigate through exercises from InterActive Physiology® and PhysioEx™, quizzes, learning activities, case studies, and other study tools that will help you succeed in A&P

Fluid, Electrolyte,

and

Acid-Base Balance

Body 1.

1034-1036)

Fluids (pp.

List the factors that determine body water content and describe the effect of each

normal cardiovascular system functioning. 11.

how

12. Explain

Indicate the relative fluid

volume and of the fluid

sodium and water

in regulating

balance.

factor.

2.

Describe mechanisms involved

compartments

potassium,

calcium, and anion balance of

solute composition

plasma

of

is

regulated.

the body. 3.

Contrast the overall osmotic

(pp.

and

effects of electrolytes

in the body.

Describe factors that

determine

1048-1055, 1058)

13. List important sources of acids

nonelectrolytes. 4.

Acid-Base Balance

fluid shifts in the

14. List the three

how

describe

Water Balance and ECF Osmolality (pp. 1036-1041) 5.

List the routes

by which water

enters and leaves the body. 6.

Describe feedback mechanisms

pH

15. Describe the influence of the

respiratory system

on acid-base

balance. 16. Describe

how

the kidneys

regulate hydrogen

hormonal controls

bicarbonate ion concentrations

water

of

and

in the blood.

Explain the importance of obligatory water losses.

8.

they resist

changes.

that regulate water intake and

output in urine. 7.

major chemical body and

buffer systems of the

body.

Describe possible causes and

consequences of dehydration, hypotonic hydration, and edema.

between acidosis and alkalosis resulting from respiratory and metabolic

17. Distinguish

Describe the importance of respiratory and renal compensations to acidfactors.

base balance. Electrolyte Balance (pp.

1041-1048)

9. Indicate the routes of

electrolyte entry

and

loss

from

18. Explain

the body. 10. Describe the importance of ionic

sodium

in fluid

and

electrolyte balance of the body,

and indicate

Developmental Aspects of Fluid, Electrolyte, and Acid-Base Balance (pp. 1058-1059)

its

relationship to

why

infants

and the

aged are at greater risk for fluid

and electrolyte imbalances than are young adults.

1034

Unit IV

Maintenance of the Body

you ever wondered why on certain days Have a time, while on you don't urinate for hours at

others you void every few minutes? Or why on occasion you cannot seem to quench your thirst?

These situations and many others reflect one of the body's most important functions: maintaining fluid, electrolyte,

and acid-base balance.

Cell function depends not only

on a continuous

supply of nutrients and removal of metabolic wastes, but also on the physical and chemical homeostasis of the surrounding fluids. This was recognized with style in 1857 by the French physiologist Claude Bernard,

who

said, "It is the fixity of the internal

environment which

is

and

"in-

environment" referred to by Claude Bernard and is the external environment of each cell. The ECF compartment is divisible into two subcompartments: (1) plasma, the fluid portion of blood, and (2) ternal

interstitial fluid (IF), the fluid in the microscopic

spaces between tissue cells. There are numerous other examples of ECF that are distinct from both plasma and interstitial fluid lymph, cerebrospinal fluid, humors of the eye, synovial fluid, serous fluid, secretions of the gastrointestinal tract but most of these are similar to IF and are usually considered

—

—

part of

it.

the condition of free and

independent life." In this chapter, we first examine the composition and distribution of fluids in the internal environment and then consider the roles of various body organs and functions in establishing, regulating,

compartment. The ECF constitutes the body's

altering this balance.

Composition of Body Fluids Electrolytes and Nonelectrolytes

Water serves as the universal solvent in which a

may be clasbroadly as electrolytes and nonelectrolytes. Nonelectrolytes have bonds (usually covalent bonds) that prevent them from dissociating in solution,- therefore, no electrically charged species are created when nonelectrolytes dissolve in water. Most nonelectrolytes are organic molecules glucose, lipids, creatinine, and urea, for example. In contrast, electrolytes are chemical compounds that do dissociate into ions in water. (See Chapter 2 if necessary to review these concepts of chemistry.) Because ions are charged particles, they can conduct an electrical current hence the name electrolyte. Typically, electrolytes include inorganic salts, both inorganic and organic acids and bases, and some

variety of solutes are dissolved. Solutes sified

Body

Fluids

Body Water Content you are a healthy young adult, water probably accounts for about half your body mass. However, not all bodies contain the same amount of water. Total body water is a function not only of age and body mass, but also of sex and the relative amount of body fat. Because of their low body fat and low bone mass, infants are 73% or more water (this high level of hydration accounts for their "dewy" skin, like that of a freshly picked peach). After infancy total body water declines throughout life, accounting for only about 45% of body mass in old age. A healthy young man is about 60% water; a healthy young woman about 50%. This difference between the sexes reflects the fact that females have relatively If

more body

fat

than males. Of

and all

relatively less skeletal

body

muscle

tissues, adipose tissue is

up to 20% water); even water than does fat. By contrast, bone contains more skeletal muscle is about 65% water. Thus, people with greater muscle mass have proportionately more

least hydrated (containing

—

—

proteins.

Although

all

dissolved solutes contribute to the

osmotic activity of a fluid, electrolytes have much greater osmotic power than nonelectrolytes because each electrolyte molecule dissociates into at least two ions. For example, a molecule of sodium chlo: ride (NaCl) contributes twice as many solute particles as glucose (which remains undissociated), and a molecule of magnesium chloride (MgCl 2 contributes three times as many: )

NaCl

-»

Na + +

CI"

body water.

Fluid

Compartments

Water occupies two main fluid compartments within the body (Figure 26.1). A little less than twothirds by volume is in the intracellular fluid (ICF) compartment, which actually consists of trillions of tiny individual "compartments": the cells. In an adult male of average size (70 kg, or 154 pounds), ICF accounts for about 25 L of the 40 L of body water. The remaining one-third or so of body water is outside cells, in the extracellular fluid (ECF)

(electrolyte;

two

particles)

MgCl 2

-*

Mg2+ +

2C1~

(electrolyte; three

particles)

glucose -» glucose

(nonelectrolyte;

one

particle)

Regardless of the type of solute particle, water moves according to osmotic gradients from an area of lesser osmolality to an area of greater osmolality. Thus, electrolytes have the greatest ability to cause

—

fluid shifts.

Chapter 26

Electrolyte concentrations of

body

Fluid, Electrolyte,

body water volume = 60% body weight

Total

fluids are usu-

40

expressed in milliequivalents per liter (mEq/L), of the number of electrical charges in 1 liter of solution. The concentration of any ion in solution can be computed using the equation

1035

and Acid-Base Balance

L,

ally

a

measure

Extracellular fluid

15

L,

20% body

volume =

weight

no. of

ion concentration (mg/L)

mEq/L

electrical

X

=

atomic weight of ion

charges

Intracellular fluid

25

on

L,

40% body

volume =

Interstitial fluid

volume = 12

weight

80%

one ion Thus, to compute the mEq/L of sodium or calcium ions in solution in plasma, we would determine the normal concentration of these ions in plasma, look up their atomic weights in the periodic table (see Appendix D), and plug these values into the equation:

3300 mg/L

X

Na~

1

of

L,

ECF

20% of ECF

FIGURE

26.1

The major

body. [Values are

for a

fluid

compartments of the

70-kg (154-pound) male.]

= 143 mEq/L

23

Ca 2+,

100 mg/L

X 2 =

5

and physical reactions, but they do not constitute

mEq/L

40 Notice that for ions with a single charge, 1 mEq is equal to 1 mOsm, whereas 1 mEq of bivalent ions (those with a double charge like calcium) is equal to 1/2 mOsm. In either case, 1 mEq provides the same degree of reactivity.

Comparison of Extracellular and Intracellular Fluids

neutral.

In contrast to extracellular fluids, the ICF con+ amounts of Na and Cl~. Its most

tains only small

is

potassium, and

its

major anion

is

Cells also contain substantial quantities of

soluble proteins (about three times the amount found in plasma). Notice that sodium and potassium ion concentrations in ECF and ICF are nearly opposite (Figure 26.2).

The characteristic

the two sides of cellular

distribution of these ions

membranes

on

reflects the ac-

tivity of cellular ATP-dependent sodium-potassium + pumps, which keep intracellular Na concentrations + low and K concentrations high. Renal mechanisms + can reinforce these ion distributions by secreting K + into the filtrate as Na is reabsorbed from the filtrate.

most abundant solutes in and determine most of their chemical

Electrolytes are the

body

fluids

and neutral

molecules.

97%

fats)

They account

in the ICF.

Movement

Among Compartments

quick glance at the bar graphs in Figure 26.2 reveals that each fluid compartment has a distinctive pattern of electrolytes. Except for the relatively high protein content in plasma, however, the extracellular fluids are very similar. Their chief cation is sodium, and their major anion is chloride. However, plasma contains somewhat fewer chloride ions than interstitial fluid, because the nonpenetrating plasma proteins are normally anions and plasma is electrically

abundant cation

found in the ECF are large for about 90% of the mass of dissolved solutes in plasma, 60% in the IF, and lesterol,

Fluid

A

HP0 4 2 ~.

the bulk of dissolved solutes in these fluids. Proteins and some of the nonelectrolytes (phospholipids, cho-

The continuous exchange and mixing

of

body

fluids

are regulated by osmotic and hydrostatic pressures. Although water moves freely between the compartments along osmotic gradients, solutes are un-

equally distributed because of their

size, electrical

Anything that changes the solute concentration in any compartment leads to net water flows. Exchanges between plasma and IF occur across capillary membranes. The pressures driving these fluid movements are described in detail in Chapter 19 on pp. 737-738. Here we will simply review the outcome of these mechanisms. Nearly protein-free plasma is forced out of the blood into the interstitial space by the hydrostatic pressure of blood. This filtered fluid is then almost completely reabsorbed into the bloodstream in response to the colloid osmotic (oncotic) pressure of plasma proteins. Under normal circumstances, the small net leakage that remains behind in the interstitial space is picked up by lymphatic vessels and returned to the blood. Exchanges between the IF and ICF are more complex because of the selective permeability of cell membranes. As a general rule, two-way osmotic flow of water is substantial. But ion fluxes are restricted and, in most cases, ions move selectively by active charge, or dependence

transport.

on

Movements

active transport.

of

nutrients,

respiratory

1036

Unit IV

What

0

Maintenance of the Body

the major cation

is

in

ECF?

In

ICF? What

is

the

intracellular anion counterpart of ECF's chloride ions?

160

Key

to fluids:

|=

Blood plasma

|=

Interstitial fluid

=

Key

Intracellular fluid

to symbols:

Na +

= Sodium

K+

= Potassium

Ca 2+

= Calcium

Mg 2+

=

HC0 3 -

= Bicarbonate

cr

= Chloride

HPO 4 2"

= Hydrogen phosphate

SO4 2-

= Sulfate

Magnesium

Mg 2

HCO.

cr

HP04 2" S04 2 "

Organic Protein acids

FIGURE 26.2 and

Electrolyte composition of blood plasma, interstitial fluid,

intracellular fluid.

and wastes are typically unidirectional. For example, glucose and oxygen move into the cells and metabolic wastes move out. Plasma circulates throughout the body and links

gases,

and internal environments (Figure Exchanges occur almost continuously in the 26.3). lungs, gastrointestinal tract, and kidneys. Although these exchanges alter plasma composition and volume, compensating adjustments in the other two the external

fluid

compartments follow quickly so that balance

is

(except during the first few minutes after a change in

one

of the fluids occurs). Increasing the

ECF

solute

content (mainly the NaCl concentration) can be expected to cause osmotic and volume changes in the ICF namely, a shift of water out of the cells. Conversely, decreasing ECF osmolality causes water to move into the cells. Thus, the ICF volume is determined by the ECF solute concentration. These concepts underlie all events that control fluid balance in the body and should be understood thoroughly.

—

restored.

Many factors

can change ECF and ICF volumes. Because water moves freely between compartments, however, the osmolalities of all body fluids are equal

suoiue uiaiojd

'

'

_ z *OdH

+X

\ eN

Water Balance and ECF Osmolality For the body to remain properly hydrated, water intake must equal water output. Water intake varies widely from person to person and is strongly

)

Chapter 26 As blood flows through lungs, Lungs

is

Fluid, Electrolyte,

How would

C0 2

and Acid-Base Balance

shown here be affected by

the values

drinking a six-pack of beer? (2) a fast

removed and

water

is

1037

in

(1

which only

ingested?

Feces Metabolism

10%

Foods

30%

Sweat 200

ml

Insensible losses via

700 ml

skin

2500 ml

Beverages

60%

4% 8%

1500 ml

and

lungs

28%

Urine

60%

Average output per day

Average intake per day

FIGURE 26.4 Major sources of water intake and output. When intake and output are in balance, the body adequately hydrated.

is

Intracellular fluid

The continuous mixing of body fluids. Blood plasma is the communicating medium between cells' external and internal environments. Exchanges between the plasma and tissue cells (intracellular fluid) are made through

FIGURE 26.3

the

interstitial

space.

Regulation of Water intake The Thirst Mechanism Thirst thirst

is

the driving force for water intake, but the

mechanism

is

poorly understood.

It

appears

that an increase in plasma osmolality of only results in a dry

influenced by habit, but it is typically about 2500 ml a day in adults (Figure 26.4). Most water enters the body through ingested liquids and solid foods. Body

water produced by cellular metabolism is called metabolic water or water of oxidation. Water output occurs by several routes. Water that vaporizes out of the lungs in expired air or diffuses directly through the skin is called insensible water loss. Some is lost in obvious perspiration and in feces. The balance (about 60%) is excreted by the kidneys in urine. Healthy people have a remarkable ability to maintain the tonicity of their body fluids within very

narrow limits (285-300 mOsm/L). A rise in plasma osmolality triggers (1) thirst, which prompts us to drink water, and (2) release of antidiuretic hormone (ADH), which causes the kidneys to conserve water and excrete concentrated urine. On the other hand, a decline in osmolality inhibits both thirst and ADH release, the latter followed by output of large vol-

umes

of dilute urine.

thirst center.

mouth and

2-3%

excites the hypothalamic

A dry mouth occurs because the rise in

plasma oncotic pressure causes

less fluid to leave the bloodstream. Because the salivary glands obtain the water they require from the blood, less saliva is produced. The same response is produced by a decline in blood volume (or pressure). However, because a substantial decrease (10-15%) is required, this is the less potent stimulus. The hypothalamic thirst center is stimulated when its osmoreceptors lose water by osmosis to the hypertonic ECF, or are excited by baroreceptor inputs, angiotensin II, or other stimuli. Collectively, these events cause a subjective sensation of thirst,

9ui Aq paja.oxa

pue speuj aq p/no/w suun

dojp p/no/w lusi/oqejaiu pue spooj jaje/w

p

dbeiudojad

jaijBiu. e

sss-j '/(|/eo/;sejp

luoj} ayeiui jaje/w .'a>/ejui

}udsajddj p\noM dyeiui a6eja

-Aag (z) fpajejjsn/f/ jou ajnoj indino ue 'paqiquji se/w /ouoo/e ipniu oo} ji 'i/ujoA ui sdeujad pue) auun w jndjno jajeM jBieajB uonuj '.sd6ej9A9q

uuojj.

eyeiui JdieM sjouj LpnjAj (i)

1038

Maintenance of the Body

Unit IV

What effect would eating mechanism?

pretzels have on this

which motivates us to get a drink (Figure 26.5). This me'chanism helps explain why it is that some cocktail lounges and bars provide free salty snacks to their patrons.

Plasma osmolality

f

1

|

Plasma volume*

Blood pressure

Curiously, thirst is quenched almost as soon as drinking water, even though the water has

we begin

yet to be absorbed into the blood. The damping of thirst begins as the mucosa of the mouth and throat is moistened and continues as stretch receptors in the

stomach and intestine

are activated,

providing feedback signals that inhibit the thirst

This premature quenching of thirst prevents us from drinking more than we need and overdiluting our body fluids, and allows time for the osmotic changes to come into play as regulacenter.

|

Osmoreceptors in hypothalamus

Saliva

JG

cells in

kidney

tory factors. Renin-angiotensin

mechanism

As

effective as thirst

indicator of need. This

Dry mouth

athletic events,

when

fore sufficient liquids Angiotensin

II

|

1 .J Hypothalamic thirst

drink

mouth, throat; stretches stomach,

I Water absorbed tract

T Plasma osmolality ("Minor stimulus)

Key: Increases, stimulates inhibits

stimulus

]

Initial

j

Physiological response

j

can be satisfied long behave been drunk to maintain

thirst

the body in top form. Additionally, elderly or confused people may not recognize or heed thirst signals, and fluid- overloaded renal or cardiac patients may feel thirsty despite their condition.

(

intestine

[

reliable

water loss includes the insensible water losses described above, water that accompanies undigested food residues in feces, and a minimum daily sensible water loss of 500 ml in urine. Obligatory water loss in urine reflects the facts that 1 when we eat an adequate diet, our kidneys must excrete 900-1200 mOsm of solutes to maintain blood homeostasis, and (2) human; kidneys must flush urine solutes (end products of metabolism and so forth) out of the body in water. Beyond obligatory water loss, the solute concentration and volume of urine excreted depend on fluid intake, diet, and water loss via other avenues. For example, if you perspire profusely on a hot day, much less urine than usual has to be excreted to maintain water balance. Normally, the kidneys begin to eliminate excess water about 30 minutes after it is ingested. This delay reflects the time required to inhibit ADH release. Diuresis reaches a peak in 1 hour after drinking and then declines to its lowest

Water moistens

Reduces,

not always a

particularly true during

Output of certain amounts of water are unavoidable. Such obligatory water losses help to explain why we cannot survive for long without drinking. Even the most heroic conservation efforts by the kidneys cannot compensate for zero water intake. Obligatory

Sensation of thirst; person takes a

|

is

Regulation of Water Output

center

from Gl

is, it is

)

level after 3 hours.

Result

FIGURE 26.5 The thirst mechanism for regulating water intake. The major stimulus is reduced osmolality of blood plasma. (Not depicted.)

all

effects of

ADH

and angiotensin

II

are

H

'jsjiqj

Buiseajoui sntji 'uoije/w/es ssajdap p/no/w upiu/w

'asesjou; p\noN\ Ai\\e\oujso

poojq

'/fyes

9je s/azjajd asneoag

-

Chapter 26

The body's water volume

is

closely tied to a

Fluid, Electrolyte,

At what point

pow-

water "magnet," ionic sodium. Moreover, our maintain water balance through urinary output is really a problem of sodium and water balance because the two are always regulated in tandem by mechanisms that serve cardiovascular function and blood pressure. However, before deal+ ing with Na issues, we will recap ADH's effect on water output.

ity

erful

and Acid-Base Balance

in this

flowchart

1039

would plasma osmolal-

change dramatically?

ability to

Influence of

Osmolality Na + concentration in

ADH

Plasma volume BP (10 - 15%)

Stimulates

The amount

water reabsorbed in the renal colrelease. When proportional to levels are low, most of the water reaching the collecting ducts is not reabsorbed but simply allowed to pass through because the number of aquaporins in the luminal membranes of the prinlecting ducts

plasma

of

ADH

is

ADH

cipal cells is at a

minimum. The

Osmoreceptors in hypothalamus

result is dilute

urine and a reduced volume of body fluids. When levels are high, aquaporins are inserted in the

Negative feedback

ADH

principal cell luminal

Inhibits

inhibits

membranes and

nearly all of reabsorbed; a small volume of

Baroreceptors

the filtered water is concentrated urine is excreted.

in

Stimulates

atrium and

large vessels

Osmoreceptors of the hypothalamus sense the solute concentration and trigger or inhibit ADH release from the posterior pituitary accord-

ECF

Stimulates

A

decrease in ECF osmolality inhibits release and allows more water to be + excreted in urine, restoring normal Na levels in the blood. An increase in ECF osmolality stimulates release both directly by stimulating the hypothalamic osmoreceptors and indirectly via the renin-angiotensin mechanism. (The latter stimulus is not illustrated in Figure 26.6 but is shown in Figure 26.9.) secretion is also influenced by large changes in blood volume or blood pressure. Under these conditions, baroreceptors in the atria and various blood vessels sense a decrease in BP and reflexively trigger an increase in secretion from the posterior pituitary. The key word here is "large" because changes in ECF osmolality are much more important as stimulatory or inhibitory factors. Factors that trigger release by reducing blood volume include prolonged fever; excessive sweating, vomiting, or diarrhea; severe blood loss; and traumatic burns. Figure 26.9 summarizes how renal mechanisms involving aldosterone, angiotensin II, and tie into overall controls of blood volume and blood pressure. ingly (Figure 26.6).

Posterior pituitary

ADH

ADH

Releases

ADH

Antidiuretic

hormone (ADH)

Targets

ADH

Collecting ducts of

kidneys

ADH

Effects

Water reabsorption

ADH

Results

in

ADH

Scant urine

Osmolality

Plasma volume

i

Disorders of Water Balance Few people really appreciate the importance of water in keeping the body's "machinery" working at peak efficiency.

The

principal abnormalities

of

FIGURE 26.6

Mechanisms and consequences of

ADH

release.

water

H

-uojidjosqe jaje/w paseajoui

i\/

1040

Unit IV

Maintenance of the Body

Hypotonic Hydration When the ECF osmolality

starts to drop (usually this + deficit of Na ), several compensatory

a

reflects

mechanisms and

hibited,

are set into motion.

as a result, less water is reabsorbed

excess water urine. But,

ADH release is in-

when

there

is

renal insufficiency or

an extraordinary amount

of

water

is

Mechanism

tonic hydration

of dehydration

is

diluted

water tion

—

its

may

when

drunk very

quickly, a type of cellular overhydration called (a)

and

quickly flushed from the body in

is

hypo-

occur. In either case, the

sodium content

is

ECF

normal, but excess

present. Thus, the hallmark of this condi+ hyponatremia (low ECF Na ), which pro-

is

is

motes net osmosis into the tissue cells, causing them to swell as they become abnormally hydrated (Figure 26.7b). These events must be reversed quickly for example, by intravenous administration of hypertonic mannitol, which reverses the osmotic gradient and "pulls" water out of the cells.

—

(b)

Mechanism

Otherwise, the resulting electrolyte dilution leads to severe metabolic disturbances evidenced by nausea, vomiting, muscular cramping, and cerebral edema. Hypotonic hydration is particularly damaging to neurons. Uncorrected cerebral edema quickly leads to disorientation, convulsions, coma, and death.

of hypotonic hydration

FIGURE 26.7

Disturbances

in

water balance.

Edema balance are dehydration, hypotonic hydration, and edema, and each of these conditions presents a special set of

problems

Edema

(e-de'mah; "a swelling") is an atypical accumulation of fluid in the interstitial space, leading to

tissue swelling.

for its victims.

that steps ders

Dehydration

When

water output exceeds intake over a period of

time and the body is in negative fluid balance, the result is dehydration. Dehydration is a common sequel to hemorrhage, severe burns, prolonged vomiting or diarrhea, profuse sweating, water deprivation, and diuretic abuse. Dehydration may also be caused by endocrine disturbances, such as diabetes mellitus or diabetes insipidus (see Chapter 16). Early signs and symptoms of dehydration include a "cottony" or sticky oral mucosa, thirst, dry flushed skin, and decreased urine output (oliguria). If prolonged, dehydration may lead to weight loss, fever, and mental confusion. Another serious consequence of water loss from plasma is inadequate blood volume to maintain normal circulation and ensuing hypovolemic shock. In all these situations, water is lost from the ECF (Figure 26.7a). This is followed by the osmotic movement of water from the cells into the ECF, which equalizes the osmolality of the extracellular and intracellular fluids

even though the

total fluid

volume

has been reduced. Though the overall effect is called dehydration, it rarely involves only a water deficit, because most often electrolytes are lost as well.

its

Edema may be caused by any event

up the flow

of fluid out of the blood or hin-

return.

Factors that accelerate fluid loss from the blood

include increased blood pressure and capillary permeability. Increased capillary hydrostatic pressure

can result from incompetent venous valves, localized blood vessel blockage, congestive heart failure, or high blood volume. Whatever the cause, the abnormally high capillary hydrostatic pressure intensifies filtration at

the capillary beds.

Increased capillary permeability is usually due to an ongoing inflammatory response. Recall from p. 789 that inflammatory chemicals cause local capillaries

to

amounts

become very porous, allowing

large

of exudate (containing not only clotting

proteins but also other plasma proteins, nutrients,

and immune elements) to form. Edema caused by hindered fluid return to the blood usually reflects an imbalance in the colloid osmotic pressures on the two sides of the capillary membranes. For example, hypoproteinemia (hi"popro"te-i-ne'me-ah), a condition of unusually low levels of plasma proteins, results in tissue edema because protein-deficient plasma has an abnormally low colloid osmotic pressure. Fluids are forced out of the capillary beds at the arterial ends by blood

Chapter 26

pressure as usual, but fail to return to the blood at the venous ends. Thus, the interstitial spaces be-

come congested with

Hypoproteinemia

fluid.

may

result from protein malnutrition, liver disease, or glomerulonephritis (in which plasma proteins pass through "leaky" renal filtration membranes and are

Fluid, Electrolyte,

and Acid-Base Balance

1041

trointestinal disorders can lead to large salt losses in feces or vomitus. Thus, the flexibility of renal mech-

anisms that regulate the

electrolyte balance of the

blood is a critical asset. Some causes and consequences of electrolyte imbalances are summarized in Table 26.1.

lost in urine).

Although the cause differs, the result is the same when lymphatic vessels are blocked or have been surgically removed. The small amounts of plasma proteins that seep out

of the

bloodstream

are not returned to the blood as usual.

As the

leaked proteins accumulate in the IF, they exert an ever-increasing colloid osmotic pressure, which draws fluid from the blood and holds it in the interstitial space. Because excess fluid in the interstitial space increases the distance nutrients and oxygen must diffuse between the blood and the cells,

edema can impair tissue function. However, the most serious problems resulting from edema affect the cardiovascular system.

When

HOMEOSTATIC IMBALANCE Severe electrolyte deficiencies prompt a craving for salty foods and often exotic foods, such as smoked

meats or pickled eggs. This is common in those with Addison 's disease, a disorder entailing deficient mineralocorticoid hormone production by the adrenal cortex. When electrolytes other than NaCl are deficient, a person may even eat substances not usually considered foods, like chalk, clay, starch, and burnt match tips. This appetite for abnormal substances is

•

called pica.

fluid leaves the

bloodstream and accumulates in the interstitial space, both blood volume and blood pressure decline and the efficiency of the circulation is severely

The Central Role of Sodium in Fluid and Electrolyte Balance

impaired.

Sodium holds

a central position in fluid

and

and

elec-

body homeostasis. Insodium input and output is one of the most important renal functions. The salts NaHC0 3 and NaCl account for 90-95% of all solutes in the ECF, and they contribute about 280 mOsm of the total ECF solute concentration (300 mOsm). At its normal plasma + concentration of about 142 mEq/L, Na is the single most abundant cation in the ECF and the only one trolyte balance

overall

deed, regulating the balance between

Electrolyte Balance and bases, but the term electrolyte balance usually refers to the salt balance in the body. Salts are important in controlling fluid movements and provide minerals essential for excitability, secretory activity, and membrane permeability. Although many electrolytes are crucial for cellular activity, here we will specifically examine the regulation of sodium, potassium, and calcium. Acids and bases, which are more intimately involved in determining the pH of body fluids, are considered Electrolytes include salts, acids,

in the next section. Salts enter the

body

in foods

and

fluids,

and

small amounts are generated during metabolic activity. For example, phosphates are liberated during catabolism of nucleic acids and bone matrix. Obtaining enough electrolytes is usually not a problem. Indeed, most of us have a far greater taste than need for salt. We shake table salt (NaCl) on our food even though natural foods contain ample amounts and processed foods contain exorbitant quantities. The taste for very salty foods is learned, but some liking for salt may be innate to ensure adequate intake of these two vital ions. Salts are lost feces,

and urine.

spiration

more

salt

is

from the body in perspiration,

When we

more

dilute.

are salt-depleted, our per-

Even

than usual can be

so,

on

a hot day

lost in sweat,

much

and

gas-

exerting significant osmotic pressure. Additionally, cellular

plasma membranes

Na +

are relatively

imperme-

but some does manage to diffuse in and must be pumped out against its electrochemical gradient. These two qualities give sodium the primary role in controlling ECF volume and water distribuable to

,

tion in the body.

important to understand that while the of the body may change, its ECF concentration normally remains stable because of immediate adjustments in water volume. Remember, water follows salt. Furthermore, because all body fluids are in osmotic equilibrium, a change in + plasma Na levels affects not only plasma volume and blood pressure, but also the ICF and IF volumes. In addition, sodium ions continuously move back and forth between the ECF and body secretions. For + example, about 8 L of Na -containing secretions (gastric, intestinal, and pancreatic juice, saliva, bile) are spewed into the digestive tract daily, only to be almost completely reabsorbed. Finally, renal It

is

sodium content

1042

Unit IV

TABLE

26.1

^

Maintenance of the Body

Causes and Consequences of Electrolyte Imbalances

Abnormality

Consequences

Possible Causes

Ion

(Serum Value)

Sodium

Hypernatremia (Na excess in ECF: >

+

Dehydration; individuals;

uncommon

may occur

in

in

healthy

infants or the

confused aged (individuals unable to

145mEq/L)

indicate thirst) or

may be

a result of

Thirst:

CNS

dehydration leads to confusion

and lethargy progressing to coma; increased neuromuscular irritability evidenced by twitching and convulsions

excessive intravenous NaCI administration +

Hyponatremia (Na deficit in

ECF: 6 mEq/L)

due to

renal failure;

hypoparathyroidism; major tissue trauma

Hypophosphatemia

Decreased

(HP0 4 2 ~

urinary output; hyperthyroidism

deficit in

No

direct clinical

symptoms because an

excess or deficit

in

accompanied by 2+ levels Ca

a

phosphate

is

usually

decrease or increase

in

intestinal absorption; increased

ECF: 105 mEq/L)

Calcium

or

1 1

(decreased excretion); malignancy; Paget's disease; Cushing's disease accompanied by osteoporosis

mg%)* 2+

Hypocalcemia (Ca deficit in ECF: -

Kidney tubules


weak base

acid

The net result is replacement (NaOH) by a weak one (NaHC0 3 the solution rises very

H20

+

water

of a strong base ),

so that the

pH of

little.

Although the bicarbonate salt in the example is sodium bicarbonate, other bicarbonate salts function in the

same way because the

tant ion, not the cation

HC0 3 ~

it is

is

the impor-

paired with. In

cells,

+

where little Na is present, potassium and magnesium bicarbonates are part of the bicarbonate buffer (a)

system.

The

buffering

power

of this type of

system

(b)

is di-

rectly related to the concentrations of the buffering

FIGURE

substances. Thus,

acids,

if

acids enter the blood at such a

rate that all the available

HC0 3

,

often referred to

as the alkaline reserve, are tied up, the buffer sys-

tem becomes

ineffective

and blood

pH

changes.

The

bicarbonate ion concentration in the ECF is normally around 25 mEq/L and is closely regulated by the kidneys. The concentration of H 2 C0 3 is just over 1 mEq/L but the supply of carbonic acid (which comes from the C0 2 released during cellular respiration) is almost limitless, so obtaining that member of the buffer pair is usually not a problem. The carbonic acid content of the blood is subject to respiratory controls.

Phosphate Buffer System The operation of the phosphate

buffer system

The

of the

).

,

weak

Again,

weak

H+

base.

+

Na 2 HP0 4 weak base

strong acid

and strong bases are converted

NaOH strong base

+

NaH 2 P0 4 weak

to water, the strong acid HCI

dissociates completely into

is

tied

up

in

acid

NaH 2 P0 4 + NaCl weak to

its

ions (H

H 2 C0 3

+

and

-

CI

),

(b)

By

weak acid, is very incomplete, and some molecules of H 2 C0 3 remain undissociated (symbols shown in green circles) in solution. contrast, dissociation of

,

a

Because the phosphate buffer system

low concentrations

in the

ECF

present in

is

(approximately one-

sixth that of the bicarbonate buffer system),

it is rel-

unimportant for buffering blood plasma. However, it is a very effective buffer in urine and in ICF, where phosphate concentrations are usually atively

Protein Buffer System Proteins in plasma and in cells are the body's plentiful

and powerful source

acid

of buffers,

most

and consti-

tute the protein buffer system. In fact, at least

three-quarters of

all

ids resides in cells,

released by strong acids

acids:

HC1

weak

Dissociation of strong and

is

phosphate system are the sodium salts of dihydrogen phosphate (H 2 P0 4 ~) and monohydrogen phosphate (HP0 4 2 NaH 2 P0 4 acts as a weak acid. Na 2 HP0 4 with one less hydrogen atom, acts as a

1

When added

higher.

nearly identical to that of the bicarbonate buffer.

components

26.1

(a)

the buffering power of body flu-

and most

of this reflects the

buffering activity of intracellular proteins.

As described in Chapter 2, proteins are polymers amino acids. Some of the linked amino acids have exposed groups of atoms called organic acid cf

salt

weak bases:

Na 2 HP0 4 weak base

+

H 20 water

dn Bui/i Aq JS^nq

e se

pe p\noM

ji

asneoaq 'sseq >/eaM y

1050

Maintenance of the Body

Unit IV

(carboxyl) groups ( + when the lease

— COOHj, which dissociate to

H

R

#

pH

— COOH

begins to

rise:

R— COCT

-»

re-

+

Notice also that the right side of the equation

H+

.

-NH

+

3

:

R— NH

+

2

H + - R— NH 3 +

hydrogen ions from the solution, it prevents the solution from becoming too acidic. Consequently, a single protein molecule can function reversibly as either an acid or a base depending on the pH of its environment. Molecules with this ability are called amphoteric molecules Because this removes

free

(am"fo-ter'ik).

Hemoglobin of red blood cells is an excellent example of a protein that functions as an intracellular buffer. As explained earlier, C0 2 released from the tissues forms H 2 C0 3 which dissociates to liberate H + and HC0 3 in the blood. Meanwhile, hemoglobin is unloading oxygen, becoming reduced hemo+ globin, which carries a negative charge. Because H rapidly binds to the hemoglobin anions, pH changes are minimized. In this case, carbonic acid, a weak acid, is buffered by an even weaker acid, hemoglobin. ,

Respiratory Regulation of H

+

In healthy individuals,

the body's chemical buffers described in Chapter 22, the respiraall

C0 2

is

expelled from the

same rate it is formed in the tissues. During carbon dioxide unloading, the reaction shifts + generated from carbonic acid is to the left, and H reincorporated into water. Because of the protein + buffer system, H produced by C0 2 transport is not allowed to accumulate and has little or no effect on blood pH. However, when hypercapnia occurs, it activates medullary chemoreceptors (via cerebrospinal fluid acidosis promoted by excessive accumulation of C0 2 that respond by increasing respiratory rate + and depth. Additionally, a rising plasma H concentration resulting from any metabolic process excites lungs at the

)

the

respiratory

center

indirectly

(via

peripheral

chemoreceptors) to stimulate deeper, more rapid

As ventilation increases, more C0 2 is removed from the blood, pushing the reaction to the + concentration. left and reducing the H respiration.

When

blood

pH

rises,

the respiratory center

is

depressed. As respiratory rate drops and respiration becomes shallower, C0 2 accumulates; the equilib+ rium is pushed to the right, causing the H concentration to increase. Again blood pH is restored to the normal range. These respiratory system-mediated corrections of blood

Respiratory system regulation of acid-base balance provides a physiological buffering system. Although such a buffer system acts more slowly than a chemical buffer system, it has one to two times the buffering power of

is

equivalent to the bicarbonate buffer system.

Other amino acids have exposed groups that can act + For example, an exposed as bases and accept H -NH 2 group can bind with hydrogen ions, becoming

an increase in any of these chemical species pushes the reaction in the opposite direction.

equilibria,

pH

are accomplished within a

minute or so. Changes in alveolar ventilation can produce dramatic changes in blood pH far more than is

—

needed. For example, a doubling or halving of alveolar ventilation can raise or lower blood pH by about 0.2

pH

unit.

Because normal

arterial

pH pH

is

7.4, a

ated by cellular respiration enters erythrocytes in the circulation and is converted to bicarbonate ions for

of 7.6 or change of 0.2 pH unit yields a blood 7.2 both well beyond the normal limits of blood pH. Actually, alveolar ventilation can be increased about 15-fold or reduced to zero. Thus, respiratory controls of blood pH have a; tremendous reserve

transport in the plasma:

capacity.

combined. As tory system eliminates replenishing

its

C0 2 supply of 0 2

.

from the blood while Carbon dioxide gener-

carbonic

anhydrase

C0 2

+

H20

7

H 2 C0 3 carbonic acid

The

H+

+

HC0 3 "

bicarbonate ion

double arrows indicates a reversible equilibrium between dissolved carbon dioxide and water on the left and carbonic acid on the right. The second set indicates a reversible equilibrium between carbonic acid on the left and hydrogen and bicarbonate ions on the right. Because of these first set of

—

Anything that impairs respiratory system functioning causes acid-base imbalances. For example, net carbon dioxide retention leads to acidosis; hyperventilation, which causes net elimination of 2

C0

Note that R indicates the

tains

many

atoms.

rest of the organic molecule,

which con-

alkalosis.

When

Renal Mechanisms of Acid-Base Balance buffers can tie up excess acids or bases tembut they cannot eliminate them from the porarily, body. And while the lungs can dispose of the volatile

Chemical

*

,

the cause of the pH imbalance is respiratory system problems, the resulting condition is either respiratory acidosis or respiratory alkalosis (see Table 26.2 on p. 1054).

can cause

Chapter 26 Reabsorption of filtered HC0 3 " is secretion. (Numbers by reaction lines indicate the sequence of events.) (T) CO2 combines with water within the tubule cell, forming H 2 CO a (D H 2 C0 3 is quickly split, forming H and HCO3 f secreted into the filtrate, a bicarbonate ion (3) For each H

FIGURE 26.12 + coupled to H

Fluid, Electrolyte,

and Acid-Base Balance

1051

Filtrate in

tubule

lumen

.

'

.

(HC0 3 ~)

enters the peritubular capillary blood by

Na

cotransport (either via symport with

f

or via antiport with

CD. (?)

can combine with

Secreted

tubular

filtrate,

HCO3

present

in

forming carbonic acid (H 2 C0 3 ). Thus,

disappears from the

the

filtrate at

(formed within the tubule

cell)

is

same

the

HCO3

HC0 3

rate that

-

~

entering the peritubular

capillary blood.

© The H C0 formed carbon dioxide and © Carbon dioxide then 2

in

3

the

filtrate

dissociates to release

water.

acts to trigger further

H

diffuses into the tubule H

cell,

where

it

secretion.

Primary active transport processes are indicated by solid red reaction arrows; secondary active transport

is

indicated by a

dashed red arrow; passive processes (simple diffusion and facilitated diffusion) are indicated

by blue arrows.

*The breakdown of H 2 C0 3 to CO2 and H 2 0 in the tubule lumen alyzed by carbonic anhydrase only in the PCT.

is

catj>

= Primary active transport

•

= Passive transport (diffusion)

»

^ = Secondary

active transport

= Protein

carrier

(CA)= Carbonic anhydrase

C0

acid carbonic acid by eliminating only the 2 kidneys can rid the body of other acids generated by cellular metabolism: phosphoric, uric, and lactic acids,

,

and ketone bodies. These acids are sometimes

metabolic (fixed) acids, but this terminology is both unfortunate and incorrect because C0 2 and hence carbonic acid are also products of metabolism. Additionally, only the kidneys can regulate blood levels of alkaline substances and renew chemi+ cal buffers that are used up in regulating H levels in + ~, the ECF. (HC0 3 which helps regulate H levels, is referred to as

from the body when C0 2 flushes from the lungs.) Thus, the ultimate acid-base regulatory organs are the kidneys, which act slowly but surely to compensate for acid-base imbalances resulting from variations in diet or metabolism or from disease. The most important renal mechanisms for regulating acid-base balance of the blood involve (1) conserving (reabsorbing) or generating new HCO3 and (2) excreting HC0 3 ~. If we look back lost

,

equation for the operation of the carbonic acid-bicarbonate buffer system of the blood, it is ~ from the body proobvious that losing a 3 + duces the same net effect as gaining a H because it + pushes the equation to the right, increasing the level. By the same token, generating or reabsorbing + ~ is the same as losing because it pushes 3 at the

HC0

,

H

HC0

H

+

the equation to the left, decreasing the H level. + Therefore, to reabsorb bicarbonate, has to be + ~, secreted, and when we excrete excess 3 is retained (not secreted). Because the mechanisms for regulating acid-

H HC0

H

+

base balance depend on H being secreted into the filtrate, we consider that process first. Secretion of H + occurs mainly in the PCT and in type A inter+ calated cells of the collecting duct. The H secreted is obtained from the dissociation of carbonic acid, created from the combination of C0 2 and water within the tubule cells (Figure 26.12), a reaction + catalyzed by carbonic anhydrase. For each H se+ is reabcreted into the tubule lumen, one Na sorbed from the filtrate, maintaining the electrochemical balance. The rate of H + secretion rises and falls with C0 2

ECF The more C0 2

in the peritubular + secretion. capillary blood, the faster the rate of levels in the

H

Because blood C0 2 levels directly relate to blood pH, this system can respond to both rising and falling H + concentrations. _Notice that secreted H + can combine with HC0 3 in the filtrate, generating C0 2

and water. In

this case,

rising concentration of

H + is bound in water. The C0 2 in the filtrate creates a

steep diffusion gradient for cell,

where

it

promotes

still

its

entry into the tubule

more

H+

secretion.

1052

Maintenance of the Body

Unit IV

H 2 C0 3 splitting into the peritubular capillary Accompanying HC0 3 ^ into the blood is the

result of

blood. Na + that enters the tubule cell as + is pumped out. ~ depends on the active Thus, reabsorption of 3 + + secretion of via an ATPase and more impor+ + tantly by a Na -H antiporter, which uses the lumen- to -tubule cell Na + gradient to drive the + transport process. In the filtrate combines with " that "dis~. For each filtered filtered

H

HC0 H

H

H HC0 3

HC0 3 appears," a HC0 3 ~

generated within the tubule cells exchange. When large amounts of are secreted, correspondingly ~ enter the peritubular blood, large amounts of 3 ~ is almost and the net effect is that com3 pletely removed from the filtrate. enters the blood

— a+ one-for-one

H HC0

HC0

Generating New Bicarbonate Ions Two renal mechanisms commonly carried out by type ate

the

A intercalated cells of the collecting ducts gener-

new

HC0 3 ~

that can be added to plasma. Both

mechanisms involve renal excretion of acid, via secre+ and excretion of either H or ammonium ions in urine. Let's examine how these mechanisms differ. tion

'

Secondary active transport mmm

^= Simple diffusion

«

^= Facilitated diffusion

'

+

= Ion channel

(CA) = Carbonic anhydrase

H

26.1 3

leaves the basolateral

HC0 3 "-CI neutrality

"

in

membrane

via

an antiport carrier

exchange process which maintains the duct

HC0

H

Generation of new HC0 3 " via + buffering of excreted H by monohydrogen 2_ + phosphate (HP0 4 ). H from the dissociation of H 2 C0 3 is actively secreted by a hT-ATPase pump and combines with HP0 4 2 ~ in the lumen. HC0 3 ~ generated at the same time

FIGURE

Via Excretion of Buffered H As long as filtered bicarbonate is reclaimed (Figure 26.12), the se+ creted is not excreted or lost from the body in + ~ in the urine. Instead, the is buffered by 3 filtrate and ultimately becomes part of water molecules (most of which are reabsorbed). ~ is "used up" However, once the filtered 3 (this has usually been accomplished by the time the + collecting ducts are reached), any additional secreted is excreted in urine. More often than not, this is the case. ~ simply restores the Reclaiming filtered 3 bicarbonate concentration of plasma that exists at + the time. However, a normal diet introduces new + into the body, and this additional must be counteracted by the generation of: new (as op3 ~) which moves into the blood posed to filtered 3 to counteract acidosis. This process of alkalinizing the blood is the way the kidneys compensate for aci+ dosis. The excreted H also must bind with buffers in the filtrate. Otherwise, a urine pH incompatible + with life would result. (H secretion ceases when urine pH falls to 4.5.) The most important urine buffer is the phosphate buffer system, specifically its weak base monohydrogen phosphate (HP0 4 2 ~). The components of the phosphate buffer system filter freely into the tubules, and about 75% of the fil-

in

a

electro-

cells.

HC0

H

HC0

H

H

Conserving Filtered Bicarbonate Ions: Bicarbonate Reabsorption

HC0

HC0

Bicarbonate ions (HC0 3 ~) are an important part of the bicarbonate buffer system, the most important inorganic blood buffer. If this reservoir of base, or alkaline reserve, is to be maintained, the kidneys must do more than just eliminate enough hydrogen + ions to counter rising blood levels. Depleted ~ have to be replenished. This is stores of 3 more complex than it seems because the tubule cells _ are almost completely impermeable to the in 3 the filtrate reabsorb them. However, they cannot ~ in a rather the kidneys can conserve filtered 3 roundabout way, also illustrated in Figure 26.12. As you can see, dissociation of carbonic acid liberates + ~ as well as While the tubule cells cannot 3 ~ directly from the filtrate, they can reclaim 3 ~ generated within them as a and do shunt 3

H

HC0

HC0

—

HC0

HC0

H

HC0

HC0

.

tered phosphate

sorption

is

buffer pair

is

reabsorbed. However, their ab-

inhibited during acidosis; therefore, the

becomes more and more concentrated

as

the filtrate moves through the renal tubules. As shown in Figure 26.13, the type A intercalated cells secrete

H+

actively via a

H + -ATPase pump and via a

Chapter 26

K + -H

+

The

antiporter (not illustrated).

combines with

HP0 4

2 ,

forming

H

secreted

H 2 P0 4

Fluid, Electrolyte,

and Acid-Base Balance

1053

1

which

then flows out in urine. Bicarbonate ions generated in the cells during the same reaction move into the interstitial space via a antiport process 3 ~-C1 then move passively into the peritubular capiland lary blood. Notice again that when H is being excreted, "brand new" bicarbonate ions are added to over and above those reclaimed from the the blood filtrate. Thus, in response to acidosis, the kidneys ~ and add it to the blood (alkagenerate new 3 linizing the blood) while adding an equal amount of H + to the filtrate (acidifying the urine).

Nucleus

Filtrate in

tubule

lumen

PCT tubule

cells

J

3er/-

ubular

8

HC0

Glutamine

capillary

Glutamine Deamination,

f

oxidation,

-Glutamine

and

acidification

—

+

J!+H

)

HC0

+ Excretion Via The second and more im4 portant mechanism for excreting acid uses the ammonium ion (NH 4 + produced by glutamine metabolism in the PCT cells (Figure 26.14). For each glutamine metabolized (deaminated, oxidized, and

HCOj (new)

NH

out

in

urine

ATPase 3

)

acidified

by combination with

H+

),

two

NH 4 +

and

The HC0 3 moves through the basolateral membrane into the blood. Ammonium + ions are weak acids that donate few H at physiologtwo

HCG* 3 ~ result.

~

pH. These, in turn, are excreted and lost in urine. As with the phosphate buffer system, this

Na +

W E 3 Na

+

Tight junction

Key:

-^= Primary

active transport

Protein carrier

ical

buffering

mechanism

^= Secondary active transport

replenishes the alkaline re-

serve of the blood, because as

NH 4 +

Passive transport (simple diffusion) is

secreted the

newly made sodium bicarbonate enters the blood. Generation of new HC0 3 " via glutamine metabolism and NH 4 + secretion. PCT cells + + metabolize glutamine to NH 4 and HC0 3 ~. NH 4 (a weak + acid) is then actively secreted by occupying the H site on + + the H -Na cotransporter. The new HC0 3 ~ generated moves into the peritubular capillary blood.

FIGURE 26.14

Bicarbonate Ion Secretion

When the body is

in alkalosis, another population of

intercalated cells (type B) in the collecting ducts ex~ ~ secretion (rather than net hibit net 3 3 + reabsorption) while reclaiming to acidify the

HC0

HC0

H

blood. Overall the type "flipped"

type

A

cells

B cells can be thought of as and the HC0 3 ~ secretion

process can be visualized as the exact opposite of the ^ reabsorption process illustrated in Figure 3 26.12. However, the predominant process in the

HC0

nephrons and collecting ducts is HC0 3 ~ reabsorption, and even during alkalosis, the amount of HC0 3 excreted is much less than the amount conserved.

Abnormalities of Acid-Base Balance and alkalosis can be classed according to cause as respiratory or metabolic (Table 26.2). The methods for determining the cause of an acid-base disturbance and whether it is being compensated (whether the lungs or kidneys are taking steps to correct the imbalance) are described in A Closer Look on p. 1055.

All cases of acidosis

Respiratory Acidosis and Alkalosis Respiratory pH imbalances result from some failure of the respiratory system to perform its normal

pH-balancing

role.

dioxide (P C oJ

is

The

carbon important indicator the single most partial pressure of

adequacy of respiratory function. When respiratory function is normal, the Pco fluctuates between 35 and 45 Hg. Generally speaking, higher values indicate respiratory acidosis, and lower values of the

mm

indicate respiratory alkalosis.

Respiratory acidosis is the most common cause of acid-base imbalance. It most often occurs when a person breathes shallowly or when gas exchange is hampered by diseases such as pneumonia, cystic fibrosis, or emphysema. Under such conditions, C0 2 accumulates in the blood. Thus, respiratory acidosis is characterized by falling blood

pH and

rising Pcch-

Respiratory alkalosis results when carbon dioxide is eliminated from the body faster than it is produced, causing the blood to become more alkaline. This is a common result of hyperventilation

1054

Unit IV

TABLE

26.2

^

Maintenance of the Body

Causes and Consequences of Add-Base Imbalances

Condition and Hallmark

Metabolic acidosis

Possible Causes;

Comments

Severe diarrhea: bicarbonate-rich intestinal (and pancreatic) secretions rushed through digestive can be reabsorbed; bicarbonate ions are replaced by renal mechanisms

uncompensated

tract before their solutes

(uncorrected)

that generate

< ^ m ^^'

j^^y 4)

new bicarbonate

Renal disease:

failure of

ions

kidneys to

rid

body

of acids

formed by normal metabolic processes

Untreated diabetes mellitus: in inability

lack of insulin or inability of tissue cells to respond to insulin, resulting to use glucose; fats are used as primary energy fuel, and ketoacidosis occurs

Starvation: lack of dietary nutrients for cellular fuels; body proteins and fat reserves are used for energy both yield acidic metabolites as they are broken down for energy

—

Excess alcohol ingestion:

results in

excess acids

in

blood

High ECF potassium concentrations: potassium ions compete with H + + tubules; when ECF levels of K are high, H secretion is inhibited Metabolic alkalosis

uncompensated

> ^ m ^^'


^'~h'>7 4) " '

+

for secretion

in

renal

+

Vomiting or gastric suctioning: loss of stomach HCI requires that H be withdrawn from blood to + replace stomach acid; thus H decreases and HC0 3 ~ increases proportionately +

+

Selected diuretics: cause K depletion and H 2 0 loss. Low K directly stimulates the tubule cells to + + secrete H Reduced blood volume elicits the renin-angiotensin mechanism, which stimulates Na + reabsorption and H secretion .

Ingestion of excessive sodium bicarbonate (antacid): bicarbonate moves easily into ECF, where

enhances natural

it

alkaline reserve

Constipation: prolonged retention of feces, resulting

in

increased amounts of

HC0 3 ~

being

reabsorbed Excess aldosterone

+

+

increased amount of H aldosterone secretion is

Respiratory acidosis

uncompensated (Pco 2 >45 pH .

of

NADH

2 P

\^2NAD

+

ATP 4

+ H4

ADP-v^^ 2

NADH

+ H+

Lactate

dehydro-

4

ATP

NAD +

genase

2 Pyruvic acid (3C)

V Oxygen

OH To Krebs cycle (aerobic

pathway)

NADH

+ H+

Lactic acid (2

H - C - OH

NAD

molecules) '

Aerobic

pathway

CHo

Oxygen deficit

present

c=o

1157

produces ATP. The phosphate

Finally, glycolysis

group, with

ADP

Two Important Metabolic Pathways

1

Lactic acid

1158

Two Important Metabolic Pathways

Step

Appendix C

Two-carbon acetyl CoA

1

with oxaloacetic acid, a 4-carbon

combined compound.

is

Pyruvic acid

from glycolysis

The unstable bond between the acetyl group and CoA is broken as oxaloacetic acid binds and CoA is freed to prime another 2-carbon fragment derived from pyruvic acid. The product

the 6-carbon

is

the cycle

citric

acid, for

S-CoA C = 0 Acetyl CoA

which

named.

is

A molecule of water is removed, and another is added back. The net result is the conversion of citric acid to its isomer, isocitric

(2C)

Step 2

Oxaloacetic acid (4C)

acid.

Step 3 The substrate loses a C0 2 molecule, and the remaining 5-carbon compound is oxidized, forming a a-ketoglutaric acid and

NAD +

reducing

Citric

acid (6C)

COOH Isocitric

NADH+H 4

acid (6C)

NAD

.

Step 4

This step is catalyzed by a multi-enzyme complex very similar to the one that converts pyruvic acid to acetyl CoA. C0 2 is lost; the remaining 4-carbon

compound

oxidized by the transfer of to form NADH + FT and is then attached to CoA by an unstable bond. The product is succinyl CoA. is

electrons to

Step 5

NAD +

Substrate-level phosphorylation occurs

CoA is displaced by a phosphate group, which is then transferred to GDP to form guanosine-triphosphate (GTP). GTP is similar to step.

in this

formed when GTP donates a phosphate group to ADP. The products of this step are succinic acid and ATP.

ATP, which

a-ketoglutaric

acid (5C)

is

FADH f

another oxidative step, two hydrogens are removed from succinic acid, forming fumaric acid, and transferred to FAD to form FADH The 2

Step 6

In

^

NAD 4

NADH+H +

\

.

function of this

coenzyme

is

similar to that of

NADH + FT,

but FADH 2 stores less energy. The enzyme that catalyzes this oxidation-reduction reaction is the only enzyme of the cycle that is

embedded other

in

the mitochondrial

enzymes

dissolved

in

membrane.

All

of the citric acid cycle are

the mitochondrial matrix.

Bonds in the substrate are rearranged step by the addition of a water molecule. The product is malic acid. Step 7 in this

Step 8

The

last oxidative

step reduces

NAD + and

regenerates oxaloacetic acid, which accepts a 2-carbon fragment from acetyl CoA for another turn of the cycle. another

Krebs Cycle (Citric Acid Cycle) All but one of the steps (step 6) occur in the mitochondrial matrix. The preparation of pyruvic acid (by oxidation, decarboxyla-

and reaction with coenzyme A) to enter the cycle as acetyl CoA is shown

tion,

above the cycle. Acetyl CoA is picked up by oxaloacetic acid to form citric acid; and as it passes through the cycle, it is oxidized four more times [forming three molecules of reduced NAD (NADH + H + and one of reduced FAD )

(FADH 2 and decarboxylated twice )]

(releasing 2

C0 2

).

Energy

is

captured

in

the bonds of GTP, which then acts in a coupled reaction with ADP to generate

one molecule

of

phosphorylation.

ATP by

substrate-level

A

Appendix D

1159

Periodic Table of the Elements

Appendix D Periodic Table of the Elements Representative -(main group)elements

Representative (main group) -

elements

A

IA

VINA

1

2

1

H

1 1

2

.0079

4

5

MIA

IVA

VA

VIA

VIIA

4.003

6

7

a

9

10

3

4

5

Li

Be

B

c

9 012

10.811

12.011

13

14

11

3

He Periodic Table of the Elements

II 1 ir\

Transition metals

12

Na

Mg

OO QQn

24 305

NIB

IVB

VB

VIB

VIIB

19

20

21

22

23

24

25

1

27

26

28

16

s

Al

Si

P

MB

26.982

28.086

30 974

29

30

31

32

33

i

D.yyy

i

15

IB

VIIIB I

O

N 4 007

1

F

Ne

18.998

20.180

17

18

CI

Ar

35.453

39.948

35

36

34

K

Ca

Sc

Ti

V

Cr

Mn

Fe

Co

Ni

Cu

Zn

Ga

Ge

As

Se

Br

Kr

39.098

40.078

44 956

47.88

50.942

51.996

54.938

55.845

58.933

58.69

63.546

65.39

69.723

72.61

74.922

78.96

79.904

83.8

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

Rb

Sr

Y

Zr

Nb

Mo

Tc

Ru

Rh

Pd

Ag

Cd

In

Sn

Sb

Te

I

Xe

85.468

87.62

88.906

91.224

92.906

95.94

98

101.07

102.906

106.42

107.868

112.411

114.82

118.71

121.76

127.60

126.905

131.29

55

56

57

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

Cs

Ba

La

Hf

Ta

w

Re

Os

lr

Pt

Au

Hg

TI

Pb

Bi

Po

At

Rn

132.905

137.327

138.906

178.49

180.948

183.84

186.207

190.23

192.22

195.08

196 967

200.59

204.383

207.2

208.980

209

210

222

87

88

89

104

105

106

107

108

109

110

111

112

70

71

6

7

Fr

Ra

Ac

Rf

Db

Sg

Bh

Hs

Mt

223

226.025

227.028

261

262

263

262

265

266

Uun Uuu 269

114

116

Uub

272

277

Rare earth elements 58

59

60

61

62

69

Nd

Pm

Sm

Eu

Gd

Tb

Dy

Ho

Er

Tm

Yb

Lu

144.24

145

150.36

151.964

157.25

158.925

162.5

164.93

167.26

168.934

173.04

174.967

90

91

92

93

94

95

96

97

98

99

100

101

102

103

Th

Pa

u

Np

Pu

Am

Cm

Bk

Cf

Es

Fm

Md

No

Lr

232.038

231.036

238.029

237.048

244

243

247

247

251

252

257

258

259

262

in

either

A

or B classes.

Elements of each group of the A series have similar chemiand physical properties. This reflects the fact that members of a particular group have the same number of valence shell electrons, which is indicated by the number of the group. For example, group IA elements have one valence shell electron, group IIA elements have two, and group VA elements have five. In contrast, as you progress across a period from left to right, the properties of the elements change in discrete steps, varying gradually from the very metallic properties of groups IA and IIA elements to the nonmetallic properties seen in group VIIA (chlorine and others), and finally to the inert elements (noble gases) in group VI A. This change reflects the continual increase in the number of valence shell electrons seen in elements (from to right) within a period.

68

Pr

the groups are classified as being

left

67

140.908

The periodic table arranges elements according to atomic number and atomic weight into horizontal rows called periods and 18 vertical columns called groups or families. The elements in

1

66

Ce

Actinides

1

65

64

140.115

Lanthanides

cal

63

Class B elements are referred to as transition elements. transition

elements are metals, and

or two valence shell electrons. trons occupy

more

(In

in

All

most cases they have one

some

these elements,

distant electron shells before the

elec-

deeper

shells are filled.) In this periodic table, the colors are used to convey information about the phase (solid, liquid, or gas) in which a pure element exists under standard conditions (25 degrees centigrade and atmosphere of pressure). If the element's symbol is 1

solid black, then the red,

then

liquid.

If

it

exists as a solid.

If its

the element's symbol

exist in nature

reaction.

element

exists as a gas.

symbol

is

is

If its

symbol

dark blue, then

is

it is

green, the element does not

and must be created by some type of nuclear

a

1160

Appendix E

Reference Values for Selected Blood and Urine Studies

Appendix E Reference Values for Selected Blood

and Urine Studies The reference values ies are

common

listed for

the selected blood and urine stud-

ranges for adults, but specific "normals" are es-

tablished by the laboratory performing the analysis.

may be ing

The values

affected by a wide range of circumstances, including test-

methods and equipment used, client age, body mass, sex, medications, and extent of disease processes.

diet, activity level,

Reference values are identified

and

tional units

(given

in

in

in

both standard or conven-

the system of international

parentheses) are measurements of

Test (Sample)

(SI)

units. SI units

amount per volume

and are used

in

most countries and scientific journals. SI units moles or millimoles per liter. Most clinical lab-

are often given as oratories

standard

and textbooks in the United States use conventional or which measure mass per volume. These values

units,

are given as grams, milligrams, or milliequivalents per deciliter

or

liter. It is

anticipated that the United States

Sample types in column 1 are serum whole blood (A), and whole blood (WB).

Reference Values:

Physiological Indication

Conventional

Clinical Implications

(SI)

will

eventually use

SI units exclusively. (S),

plasma

(P), arterial

and

Blood Chemistry Studies

Ammonia

15-120

(P)

Liver

(xg/dl

(12-65 jimol/L)

Amylase

(S)

and

renal function. Increased values

in liver

newborn hemolytic disease, heart pulmonale. Decreased values in hypertension. renal failure,

56-190 IU/L

Pancreatic function. Increased values

(25-125 U/L)

mumps,

in

disease,

failure,

cor

pancreatitis,

obstruction of pancreatic duct, ketoacidosis.

Decreased values in liver disease, perforated bowel, pulmonary infarct, toxemia of pregnancy.

10-40 U/ml (5-30 U/L)

Aspartate aminotransferase

Cellular

acute

after myocardial infarction,

disease, drug toxicity, muscle trauma.

Decreased

(ALT) or glutamic-oxaloacetic

transaminase (SGOT)

damage. Increased

liver

in

ketoacidosis.

(S)

Total: 0.1-1.0

Bilirubin (S)

mg/dl

(5.1-17.0 jjumol/L)

Conjugated: Rhodopsin, 576-578, 577/, 578/

of

Sagittal suture, 203, 205,

380/ upper limbs, 362-363t, 363/

Rotator

cuff,

269

(hindbrain),

431, 432/ Rhomboid muscles, 333/, 352, 353/, 353t

Rhythm method,

Ribonucleic acid. See

RNA

molecular structure

of,

44,

45/

Ribosomal RNA, 87 Ribosomal RNA (rRNA), 105 Ribosomes, 65/, 70f, 85/, 86/, 87, 87/

membrane-bound,

87 226-228, 227/, 228/ articulations of, 258f

Ribs,

as part of axial skeleton,

Salivary glands, 125/, 882/,

87, 87/

as accessory digestive organ,

(cochlear)

window, 582,

583/, 585/, 586/

treatment,

Rickets,

883

319

193

18, 19/

Right upper quadrant (RUQ), 18, 19/

Rigor mortis, 295

RNA-DNA hybrid, 106, 107/ RNA polymerase, 106, 107/ RNA primers, 100/, 101

369r

SCID

of uterus, 1080/, 1082/,

Salts, 34, 34/, 41,

1083 (ribosomal RNA), 105

RU-486

(mifepristone), 1125/)

Rubrospinal

tracts, 477t, 478/,

Ruffini's corpuscles, 492t,

244/

407, 407/

493

Rugae, 898, 898/ urinary bladder, 1023-1024,

1025/ vaginal, 1084 Rule of eights (octet rule), 33 Rule of nines, 167, 168/ RUQ. See Right upper quadrant RV (residual volume), 849, 850/

41/ balance in body. See Electrolyte balance

found in body, 28t, 1041

555-557 Saphenous nerve, 514/ Saphenous veins, 759/, 766/, Salty taste sensation,

766t Sarcolemma, 284, 285/, 287/, 288 resting, 291,

291/

in cardiac muscle, 688/

Sarcoma, 148 Sarcomere, 282/, 282t, 284, 285/ in cardiac/skeletal/smooth

Sarcopenia, 319

Sacral arteries, 752/, 754t,

Sarcoplasm, 284 287, 287/

Sacral canal, 225/ Sacral crest, 225/

cardiac muscle, 314£, 688/

Sacral curvature, 219-220,

skeletal muscle, 3 1 4r

smooth muscle, 310, 314f

219/ Sacral foramina, 225, 225/

516t,

367f, 368/, 379r (sinoatrial) node,

517

Sacral promontory, 225, 225/,

238/

bonds, 182

Sacroiliac joint, 225, 238/,

239, 259r Sacrospinalis muscles. See

Erector spinae muscles

691-692,

691/ Satellite cells

of

Sacral region, 14/

Sacrificial

Sartorius muscle, 331/, 367,

SA

neuron 391

cell bodies, 390/,

of skeletal muscle,

318

408 706-707 Sclerotherapy, 741 Scleroses,

valvular,

Sclerotome, 1123, 1123/ Scoliosis,

Scurvy,

219-220

T48

Sebaceous

(oil)

glands, 125/,

153/, 157/, 158, 161/

Seborrhea, 158

Secondary curvatures, 248 Secondary ossification centers, 185-186, 185/ Second-class levers, 328, 329/ Second-degree burns, 167-168, 168/ Second-messenger mechanisms, 84-85, 84/ amino acid-based hormones, 606-608, 606-607/ neurotransmitters, 419, 421 Second-order neurons, 474, 475/ Secretin, 637t, 904, 905f, 916, 916/ Secretion,

Satiety

hormonal

combined

Sebum, 158

Sarcoplasmic reticulum (SR),

755/

(severe

immunodeficiency) syndromes, 818 Sclera, 561/, 564, 565/, 567/ Scleral venous sinus (canal of Schlemm), 565/, 568, 569/

Scotoma, 598 Scrotum, 1064/, 1065, 1065/ Scuba gear, 866-867b

electrical conditions of

Saccule, 584, 585/, 593/

Sacral spinal nerves, 470/, 508/

105

by,

Saltatory conduction, 404,

Sacral hiatus, 225/

of,

muscles served

270/ of liver, 912, 913/, 1134

Sacral plexus, 508/, 515, 516/,

105

cells, 390/, 391, 392/ axons and, 394-395, 394/ regeneration and, 498-499, 499/ Sciatica, 515

Sciatic notch, 237, 238/, 239,

Risorius muscle, 335f, 337/

role in protein synthesis,

Schwann

891- 892 Salpingitis, 1105

Round ligament

Ringer's solution, 670

RLQ. See Right lower quadrant RNA, 55-57 DNA compared to, 57

Schizophrenia, 484

Sciatic nerve, 515, 516/, 5 1 6r

muscle, 314t

Right lower quadrant (RLQ),

types

535/, 545t

Salivatory nuclei, 536,

204/ cartilage in, 135/

RICE

of, 891-892 927

890- 892, 891/

479

Ribose, 57, 57f

Salivary amylase,

1 4/ Scar tissue, 142, 144

891

ANS fibers/effects,

rRNA

1125fc

Riboflavin (vitamin B2), 948f

of,

reticulum), 65/, 70t, 86/,

Round

of, 25 8t, 269/ muscles acting on, 352-353t, 353/ Scapular nerve, 512£, 513/ muscles served by, 353r

Scapular region,

composition

Rough ER (endoplasmic

of femur, 241, 241/, 270,

Rhombencephalon

mechanism,

793t neural controls

muscles, 354, 355t, 356/ Rotatores muscle, 345/

205/

890

as protective

232

articulations

760/, 760t, 761/ Saliva,

nerves, 504-505t Scaphoid bone, 23 It, 236, 236/ Scapulae, 229, 229/, 230/,

231f,

Sagittal sinuses, 463/-465/,

262/

inhibitors,

free vs.

Saddle joints, 256f, 258t, 265/,

of lower limbs, 379-380t,

Reverse transcriptase of

932

Rotation (movement), 262,

422, 422/

muscles, 335t, 337/

225-226, 225/

508

(tooth),

male, 240f

regional characteristics,

160

Rosacea, 162/7

Reverse transcriptase, 8 1

R group

reflex,

Rootlets,

vs.

47

Scalene muscles, 342f, 343/ Scalp

as part of axial skeleton,

204/ in female

fats,

Scala media, 585, 586/

controls,

hypothalamic regulation

447 neural signals, 982-983

124

Secretory component, neuron,

983 of,

392/, 393, 396t Secretory IgA, 805, 805f

Secretory lysosomes, 90

9

,

1233

Index

Secretory unit of glands,

25,

1

Septal defects, 706, 707/

male, 1070

Septicemia,

88-89, 88/ Segmental arteries, 999/, 1000 Segmental branches, of cervical

Septic shock (sepsis),

78/,

Septum, deviated, 445/', 455/,

Segmental bronchi, 838-840, 838/, 842/ Segmental level, of motor hierarchy, 519, 519/ Segmentation, 883, 883/, 884/, 91 If, 920 of eye, 564, 565/,

568-569, 569/

567/,

Seizures, epileptic,

Self-antigens,

Semicircular canals, 583/, 584,

585/

886-887, 886/ stomach, 900/

hypovolemic, 738, 739/, 1009, 1040

Serous Serous

blood clotting, 662

cells,

891, 891/

fluid, 18, 18/,

140

139-140, 139/ abdominopelvic cavity, 885-886, 885/ Serous pericardium, 676, 677/

505f, 595/

Semicircular duct, 584, 585/ Semiconservative replication,

101

100/,

Serratus anterior muscle, 331/,

352f, 353/ Serratus muscles, 349/

Semilunar cartilages, 266, 267/ Semilunar (gasserian) ganglia,

Sertoli cells (sustentacular cells),

1074

Sesamoid bones, 178

503f

Semilunar

(SL) valves,

684,

Semimembranosus muscle, 333/, 371/, 372f, 379t

Seminalplasmin, 1070 Seminal vesicles, 1064, 1064/, 1068/,

1069

Seminiferous tubules, 1065, 1065/, 1066/ Semispinahs muscles, 344f,

345/ Semitendinosus muscle, 333/, 371/, 372f, 379t

493 Sense organs, 491 Sensation, 490,

general senses, 491-493,

492f See Special senses Sensible water loss, 1038 Sensorineural deafness, 592 Sensory (afferent) division of special.

PNS, 388, somatic

389/, 490/

vs. visceral

fibers of,

nerve

388, 389/

(afferent) nerves, (afferent)

497

neurons,

395, 397f Sensory input, 388, 388/ Sensory receptors, 490-493 of,

complex general,

490-491

vs. simple, 491 491-493, 492f

Sensory tunic

Set point, 10

Severe combined

685/, 686-687, 687/

(retina) of

566-568, 567/ Sentinel node, 783 eyeball,

Septal cartilage, 215/, 216,

lithotripsy,

Short-term

male, 1079 Sex chromosomes, 1097, 1140 Sex differences, in muscular development, 318 Sex hormones, 1064 growth spurt and, 946 Sex hormones

memory (STM),

of,

759/-761/, 760f ethmoid, 211, 211/, 216/ frontal, 204, 206/, 215/, 216/, 832/ lymph, 776/, 777 mastoid, 207 maxillary, 213, 216/

paranasal, 216, 216/

258f, 268-269, 269/

511, 5 1 2f

513/ muscles crossing, 354-356f, 356/ actions of (summary), 362-363f, 363/ Shoulder (pectoral) girdle, 228, 231f articulated, 230/ bones 229, 229/, 230/,

463/-465/, 760/,

sagittal,

760f, 761/

venous, 565/, 568, 569/ sigmoid, 760/, 760f, 761/ sphenoid, 206/', 209, 2 1 5/, 216/, 832/ straight, 464/, 465/ scleral

transverse, 463/, 760/, 760f,

761/ venous, 721 Sinus headache, 833 Sinusitis,

833

Sinusoids (sinusoidal

231f

capillaries), 715/', 718/,

719

scapulae, 229, 229/, 230/,

232

231f,

912, 914/ Sinus rhythm, 691 liver,

muscles acting on, 352-353f, 353/ Shuttle molecule, 965

Sinus venosus, 703, 703/ Skeletal cartilages, 176, 177/

SIADH

Skeletal

(syndrome

inappropriate

of

ADH

secretion), 617f, Sickle-cell

654/,

1059

fiber

gross, 282/, 282f

microscopic, 284-288,

1145

285/

145

Sickle-cell crisis,

628-629, 633-634

Sickle-cell trait,

1145

Sickling gene,

145

1

muscle

anatomy

anemia, 653-654,

(gonadocorticoids), 626f,

location/functions in body,

1023

Shoulder blades. See Scapulae Shoulder (glenohumeral) joint,

Sex characteristics, secondary female, 1094, 1095f

684, 721

460-461, 460/

innervation

coronary, 678, 680/, 683/, dural, 464, 464/, 721, 740,

Short bones, 178, 178/, 181 Short tandem repeat (STR), 95b

clavicles,

immunodeficiency (SCID) syndromes, 818

740 738-740

738-740

vascular,

Shock wave

of

vestibulocochlear nerve and,

831/

circulatory,

Serous membranes (serosae), 17-18, 18/, 138,

210/, 215/, 2171

Semen, 1069-1070

classes

of alimentary canal,

role in

Sella turcica, 206/, 208/, 209,

Sensory Sensory

cardiogenic,

in digestion, 905f

727/

cavernous, 464/

anaphylactic, 738-739, 820

18/, 138,

899

797-798

carotid, 506f, 726,

Shock

139-140, 139/

Serotonin, 416r, 418, 637f,

Selenium, 28f, 954f

987

Shivering,

Sinoatrial (SA) node,

691/ Sinus (bone marking), 179< Sinuses

426

Shingles,

Shin splints, 373f, 384

423

Serosae (serous membranes),

17-18,

fibers,

180/, 181, 183/

434/,

smooth muscle, 313 691-692,

Single-unit

Sharpey's (perforating)

465/

Serial neural processing,

457

792

Selectins, 655,

824 876

Septum pellucidum, 434,

plexus, 510/, 51 If

squamous, 120, 120/ Sine wave, 587, 587/

female, 1096

672

Secretory vesicles (granules),

Segments

Sexual response

Septal nuclei, 454, 455/

126/

125/",

1

cardiac muscle vs., 314f,

688-689 connective tissue sheaths,

Sex-linked inheritance,

SIDS (sudden infant death syndrome), 876

281, 283, 283/ contraction of, 289-295,

Sex organs (gonads), Sexual development,

Sigmoidal 755/

myofibrils,

48t

1146 1064

1097-1102

291/-295/ 284-287, 285/

arteries, 752/, 754f,

Sigmoid colon, 882/ Sigmoid sinuses, 760/, 760f, 761/

sarcoplasmic reticulum,

descent of gonads, 1101, 1101/

menopause,

Signal-recognition particle

T

1

102

of external genitalia, 1098,

1100, 1100/ of internal reproductive

(SRP), 87, 87/

Signal sequence, 87, 87/

Signal transduction,

organs, 1098-1101,

membrane

1099/

m, 67, 67/

puberty,

1101-1102

sex determination,

1097-1098 Sexually indifferent stage,

1098, 1099/ Sexually transmitted diseases

(STDs), 1096-1097

Silent ischemia,

protein's role

287, 287/

smooth muscle

Silicon, 28f

Simple (closed) fracture, 191 Simple diffusion, 71/, 72, 72/ Simple epitheha, 119, 119/', 120-121, 120-121/ columnar, 121, 122/ cuboidal, 121, 121/

314f

288 305-307, 306f

types

of,

Skeletal muscles, 281, 282f

aging and, 3 1

anatomy gross,

704b

vs.,

tubules, 287/,

281-284, 282f

microscopic, 284-288 surface, 330/,

332/

as source of blood glucose,

975 attachments, 283-284 direct (fleshy), indirect,

284

284 continues

8

1234

1

Index

Skeletal muscles, continued

limbs, 228-237, 231t

vs.,

muscle fibers, 289-295, 291/-295/ of whole muscles, 295-300, 296/-300/ functional classes of, 325 in men vs. women, 318 of

innervation interactions

of,

289/, 5

of,

325

length-tension relationship

304-305,

in,

major,

305/"

330-383 330/-333/

superficial,

mechanics arrangement, 326, 327/ lever systems, 326-330, 329/

fascicle

naming

criteria for,

325-326

nerve supply, 281 preferred energy source, 975r

smooth muscle

vs.,

314-315r somatic nervous system and, 388, 389/ tissue of, 140, 141/, 280 venous blood pressure and, 724, 724/ Skeletal system, 6/. See also

Bone Skeleton

288/

diaphragms, 1004, 1005/

vertebral column,

Slit

pores (filtration

219-226

Skill (procedural)

Skin,

(prolapsed) disc

memory,

28t, 952t

electrolyte balance and,

slits),

1000, 1001/, 1005/

461, 462/

625-628, 1043 dietary sources/RDAs/ importance in body, regulating,

627/,

Slit

1041, 1042f, 1043 blood pressure homeostasis,

,

2+

channels, 689-690, Slow Ca 689/ Slow fibers, speed of muscle

1044- 1045, 1044/

contraction and,

152-157

influence of

of, 169 appendages of, 157-164 as blood reservoir, 1 66

aging

164- 165, 787-788, 793/ biological barriers of, 165 blood flow, 735 at rest/during exercise,

732/ body temperature regulation by, 165

166-167 color of, 1 56-157

Slow oxidative 306t

919-920, 928/

hormones

1

influence on, 1047

wall histology, 909-910,

909/

1011-1012,

Sodium-potassium pump, 77,

402-404, 403/ in action potentials, 290,

291/ muscle

fatigue,

membrane

303

potential and,

82-83, 399-400 operation

of,

76/

Soft callus, 191, 191/ Soft palate, 830, 831/, 832/,

888/ Soleus muscle, 331/,

Smell sense, 558-560, 558/ activation of olfactory receptors,

559

332/-334/, 373, 374/-375/, 376r, 377/-378/, 379t

aging and, 596

Sol-gel transformations,

developmental aspects, 596

Solid state matter,

disorders,

76/,

404

action potentials and,

secreted by, 637t

of,

399-400

of,

1011/

in

919-920 parathyroid hormone's motility

membrane

potential,

digestive processes occurring

on, 620t

endocrine system and, 638b epidermis, 123, 152-155 excretion of wastes by, 166 general sensory receptors in, 491, 492t homeostatic imbalances of,

in resting

reabsorption

sounds of, 695, 695/ Small cell carcinoma, 871 Small intestine, 882/, 907-920 anatomy, 907-910, 908/-910/, 912 ANS fibers, 536/, 538/

functions overview, 9 1

hormone

in blood plasma/IF/ICF,

1036/

684, 686-687, 687/

in,

cutaneous sensory receptors of, 165 developmental aspects of, 169 effects of thyroid

305-307,

fibers,

Slow- wave sleep, 458, 459r SL (semilunar) valves, 681/,

cancer,

ANP

1045- 1046, 1045/

305-307, 306f

as protective barrier,

1

in body,

contraction, 288-289,

Slipped disc. See Herniated

developmental aspects, 247-248, 247/

contraction

and, 290, 291/, 402-404 aldosterone's role in

176, 203 bony thorax, 226-228 skull, 203-218

See Skeletal muscle

fiber

action potential generation

Sliding filament theory of

pelvic girdle/lower limbs,

axial,

314-315f

Sodium

erythematosus), 819

237-247, 246f

732/ blood supply, 281, 281/ body location, 314r

cells of.

460 SLE (systemic lupus Sleep apnea,

228

pectoral girdle/upper

at rest/during exercise,

cardiac muscle

aging and, 248 appendicular, 176,

283 origin, 259, 283 blood flow, 734-735 insertion, 259,

560

32

26

Solitary nucleus, 451/, 557,

;

cardiovascular system and, 742ft

developmental aspects, 196,

166-169 hormones secreted by, 636 immune system and, 787-788, 793r of, 517-518, 517/

247-248 digestive

system and, 934b

effects of thyroid

metabolic functions

of,

6/

integumentary system and,

structure

systems, 197b

systems of, 326-330, 329/ lymphatic system/immunity lever

and, 780b muscular system and, 3 1 6b, 317b nervous system and, 548b reproductive system and, 1103b, 1104b respiratory system and, 874b urinary system and, 1056b Skeleton, 202-251, 203

of,

143/

transduction mechanism, 559, 560/

developmental aspects,

247-248 fetal, 247, 247-248 joints Sleep,

of,

destruction and, 837

lung cancer and, 871 Smooth ER (endoplasmic

458-460 460

location, 3

1

1

5f

circular/longitudinal layers,

309-310, 310/

839-840

innervation, 310, 311/, 518 of,

904, 906

single vs. multiunit,

459-460 447, 459 of,

458, 459t

313

4-3 1 5r structure, 309-311, 310/ Sneezing, mechanism of, 852r skeletal vs., 3

1

31

water as universal, 40, 1034 Soma (neuron cell body), 390/, 391-392, 392/ Somatic afferent nerves, 497 Somatic efferent nerves, 497 Somatic mesoderm, 1123, 1123/ Somatic motor neurons of spinal gray matter, 473,

4f

cardiac vs., 3 1 4-3

plasticity

of,

types and stages

as type of tissue, 142, 142/

in bronchi,

253, 253/, 258t

importance

88

Smooth muscle, 280, 309-315

31-32

31

Solvents,

chronic bronchitis and, 870

contraction, 311-313, 311/

disorders,

patterns,

Smoking

body

Solutions, true,

reticulum), 65/, 70r, 86/,

991 Skull, 203-218, 204/ bones of cranial, 203-211 facial, 211-214 summary, 2 1 7—2 1 8t Skin-fold test,

557/ Solute pumps, 77 Solutes, "31

559-560

cilia

152, 153/

tissue repair in, 143-144,

170/7

interrelationships with other

of,

165- 166

endocrine system and, 638b functions

olfactory pathway, 558/,

innervation

hormone

on, 620f

nerves, 499, 500/, 501t

473/ Somatic nervous system, 388, 389/ ANS compared to, 532-534, 533/ PNS in relation to, 490/ Somatic pain, 494b Somatic recombination, 806 Somatic sensation, 437/ Somatic sensory neurons of spinal gray matter, 473,

473/

1235

Index

Somatic

vs. visceral afferent

nerve

fibers,

388, 389/

Somatomedins, 613, 614/ Somatosensory association cortex, 437/, 439-440 Somatosensory cortex, primary, 437/,

439

Somatosensory homunculus, 438/,

439

Somatosensory system, 493 circuit level processing, 496 general organization

496/

of,

perceptual level processing,

497 493, 496 Somatostatin, 4f8f, 613-614, 614/, 631

cell life cycle, 99,

lumbar, 514-515, 514/, 5141

99/

Sphenoid bone, 209-210, 210/, 215/, 217f

5161

209 209

Spinal reflexes,

Spinal shock, 479, 521, 550 Spine, 219. See also Vertebral

column

localization

591 587-588, 587/

of,

of,

circular fascicular pattern

and, 326, 327/ esophageal, 897/

730-731 sensation, 555-557

of Korotkoff,

Sour taste Spasm, 319

as,

836

parasympathetic/sympathetic effects, 545f precapillary, 715/, 719-720, urethra, 350t, 351/, 1024/,

1025 Sphygmomanometer, 730 Spina bifida, 249, 481 Spinal cavity, 15, 17/

anatomy, 469-471, 470/

autonomic functions regulated by, 546-547,

Special senses, 491, 555-602.

479-480

disorders,

sense

embryonic development, 431-433, 432/, 469, 469/, 1119, 1121/ gray matter of, 471-473, 472/, 473/ pathways to brain

Special sensory receptors,

555

Specific ascending pathways,

474, 475/, 476t

1022 647

Specific gravity,

Speech, muscles involved in Broca's area,

439

Speed lever (mechanical

473-476 descending, 477-479 ascending,

trauma

330

white matter

Spermatic cord, 1065/, 1066, 1066/ Spermatids, 1074 Spermatocytes primary, 1074

1074

Spermatogenesis, 1070-1077,

1075/ events in seminiferous tubules,

Spermatogenic

1074-1077 cells,

1066/,

1074, 1075/ Spermatogonia, 1074 Spermiogenesis, 1074, 1076/ Sperm (spermatozoa), 1064,

1070 in fertilization,

regions,

1111-1113,

1112/ in spermatogenesis,

1074-1077, 1075/,

343r Splenomegaly, 783 Spliceosomes, 106

344t

Spongy

brachial,

510-513, 512f,

513/ cervical, 510, 51 Of, 51 If

628 hormones, 605, 624 adrenocortical, 624-629,

(penile) urethra, 1024/,

mechanism of action, 608-609 Steroids, 48, 605 anabolic, 308£>

location/function in body,

1025, 1064/, 1068/, 1069 during, 302-303, 302/ Sprains,

272 cell

586/ carcinoma,

Squamous epithelium, 119,

stratified,

Squamous

123, 123/

region, of temporal

(signal-recognition

particle), 87, 87/ (sarcoplasmic reticulum),

287, 287/ Stapedius muscle, 584, 584/ Stapes (stirrup) bone, 21

anatomy gross,

898-899, 898/

microscopic, 899-901,

900/ blood supply, 747/, 753r,

203, 205, 206/

SR

intensity and, 406, 406/ S-T interval, 694, 694/ Stirrup (stapes) bone, 583/, 584, 584/

(short-term memory), 460-461, 460/ Stomach, 882/, 897-907

bone, 207, 209/ Squamous (squamosal) suture,

SRP

48r

mechanism of action, 608-609 Stimuli, 9/, 10, 490

STM

simple, 120, 120/

nerve plexuses, 508/,

509- 510

Sternocostal joint, 254, 254/,

626t

119/

by,

accessory nerves and, 507r

Steroid

508-510

muscles served

330/, 331/, 333/, 337/,

Steroid diabetes,

508, 539/

509/ innervation of specific body

230/, 235/

Splenius muscles, 337/, 343/,

166, 167/, 871

508/',

1067

Sternal angle, 226, 227/ Sternal body, 226, 227/

Splenic veins, 759/, 777, 778/

472/

508- 510,

Stereocilia, 586/, 592, 593/,

341/ Sternum, 204/, 226, 227/, 258t

538/

Squamous

of,

Stercobihn, 652-653, 652/

753/, 753t, 777, 778/ Splenic cords, 778, 778/

fibers,

Spinal nerve roots, 220/, 470/

distribution/formation

Stents, 717/?

Splenic arteries, 747/, 752/,

Spiral organ of Corti,

Spinal nerves, 388, 389/, 471, 473, 473/, 497, 508-518

649 stomach, 901

258f Sternohyoid muscle, 331/, 340f, 341/, 343/ Sternothyroid muscle, 340t,

882/

Spinalis muscles, 344f, 345/ dorsal, 472,

lymphoid, 658, 659/ myeloid, 658, 659/ of blood's formed elements,

341/, 342f, 343/

538/, 539/, 540 Spleen, 777-779, 777f, 778/,

469

ventral, 471, 472/, 473/,

111, 147,

cells,

482-483fc>

Sternocleidomastoid muscles,

Sports activities, energy sources

Spinal dural sheath, 465/, Spinal fusion, 249

Stem

Sternoclavicular joint, 258f

Spinal curvatures, 219-220,

219/

1096-1097

Splanchnic circulation, 886 Splanchnic mesoderm,

180/, 181/, 182, 183/

473, 474/

(sexually transmitted

diseases),

Sternal region, 14/

as connective tissue, 127/

of,

592

Sternal end, of clavicle, 229,

Spongy (cancellous) bone, 179,

479

disadvantage), 328, 328/,

927

Spirometer, 851

protection, 469, 470/ to,

586/

Spiral organ of Corti, 585,

ANS

546/

See also under specific

1076/

590-591, 591/

Splanchnic nerves, 536/, 537,

497 Spatial summation, 412, 413/

STDs

594/,

Spiral ganglia, 505f, 586/,

1123-1124, 1123/

469-480

479

Static equilibrium,

Spiral fracture, 192f

585/, 586/, 591/

Spatial discrimination, 439,

secondary,

474, 475/, 476f Spinous process, 219/-224/, 221, 222f Spiral (coiled) arteries, 1084, 1084/

Spinal cord, 388, 389/,

Spastic paralysis,

Spectrin, 52r,

476, 476t, 496 Spinothalamic pathways/tracts,

Spiral lamina, 585,

719/

of,

449

Steady state, 82

pathways/tracts, 475/,

923

anal, 350r, 351/, 921/,

larynx acting

Sonography (ultrasound imaging), 20b, 1135 Sound, 582, 585, 587. See also Hearing

521-526

Spinal region, 14/

Spine (bone marking), 179f Spinocerebellar

(hepatopancreatic sphincter), 908, 908/

46

chemical digestion

maculae and, 592-593, 593/ Statin drugs, 982 bone density and, 1 94

509/

Sphenoid fontanel, 247/ Sphenoid processes, 212/, 213 Sphenoid sinuses, 206/, 209, 215/, 216/, 832, 832/ Sphincter of Oddi

583/, 584, 584/, 585/

Starches,

Startle reflex,

rami distribution, 508-510,

greater wing, 208/, lesser wing, 208/,

515-517, 516/,

sacral,

gastroesophageal, 895, 897/ hepatopancreatic, 908, 908/

in digestion, 899, 905f Somatotopy, 438, 473 Somatotropic cells, 613 Somite, 1123, 1123/

properties

phase of

Sphincters

receptor level processing,

Sounds

S

8t,

764-765f curvatures

of,

898, 898/

digestive processes occurring in,

901-907 continues

,

1236

,

Index

Stomach, continued functions overview, 9 1 gastric emptying,

1

(

906-907,

907/ gastric secretions,

902-904,

902/, 903/

gross anatomy, 898-899,

898/

hormones

467-468

Stroke, 419, 439,

secreted by, 637f,

Stroke

innervation, 535/, 536/,

698-699,

(SV),

698/, 699/ blood pressure and, 724-725, 725/ cardiac output and, 701/ Stroma, 133, 775, 843 Strong acids, 43, 1048, 1049/ Strong bases, 43

STR

905f

volume

(short

tandem

repeat),

95b

Structural (fibrous) proteins, 50, 52f

537, 538/, 539/, 540,

Stuart factor, 66 It

899 motility, 545f, 904,

Student's elbow, 273

906-907, 906/ mucosa, 122/, 898, 898/, 900/, 901

Stupor (consciousness

Stomach (gastric) glands, 125/ Stomodeum, 932, 933/

state),

458 Stuttering, Sty,

876

562

Supporting

Submucosal plexus, 886/, 887-888, 900/ Subscapular

arteries, 750/,

of hearing, 586/ of olfactory receptors, 558/,

354, 355r, 356/

362-363t, 363/ tendon, 269/ Subscapular nerves, 512t, 513/ muscles served by, 355f Substance E 417t, 418, 494b Substance (vesicular)

450/

Strabismus, 502f, 504r, 564 Straight arteries, 1084, 1084/

Stylohyoid muscle, 339/, 340?

957, 957/, 958/, 959 Substrates, 53/, 54, 55/

760/, 760t, 761/

Styloid process

Strain,

234/ temporal bone, 206/, 207,

radius, 234,

320

Strata of epidermis, 153-155,

208/, 209/, 217f, 339/,

154/

341/

Stratified epithelia, 119, 119/,

121, 123-124, 123-124/

Stratum basale (basal layer), 153-154, 154/ Stratum basalis, of endometrium, 1083, 1084/ Stratum corneum (horny layer), 154/, 155 Stratum functionalis, endometrium, 1083, 1084/ Stratum germinativum. See Stratum basale Stratum granulosum (granular layer), 154/, 155 Stratum lucidum (clear layer), 155 Stratum spinosum (prickly layer), 154-155, 154/ Streamlining, 722 Stress incontinence, 1027,

1131 to,

1

90,

1

90/

Stress proteins, 53

Stress-relaxation response,

Stretch, muscle. See

Muscle

Stretch receptors, 490, 492f Stretch reflex, 521-525, 523/

156 See Visual

cortex Striated Striate.

muscle

tissue,

40

285/ vascularis, 585, 586/

Striations, 280, 284, Stria

1

See Visual cortex

157-158, 157/ Sugars

45/,

747/, 749/, 750/, 750t,

751/ Subclavian trunks, 773, 774/ Subclavian veins, 758/-763Z,

758t lymphatic vessels and, 774/ Subclavius muscle, 352f, 353/ nerve to, 513/ Subcostal arteries, 75 It

510

Subcutaneous prepatellar bursa, 266, 267/ Subdural hemorrhage, 467 Subdural space, 464, 472/

ANS

fibers, 535/, 536/,

Monosaccharides

Submandibular ganglia, 504f 536, 536/ Submandibular gland, 504f, 882/, 888/, 890, 891/ ANS fibers, 535/, 536/, 538/

Submucosa esophageal, 895/ of alimentary canal,

886-887, 886/

434, 435/, 436, 437/, 440, 449/

470/

Sulcus terminalis, 889-890,

890/ blood

sources/RDAs/ importance in body, 28r, 952f Summation, 412-413, 413/ Sun exposure damage to skin, 156 Sulfur, dietary

226, 227/ Sural

(calf)

region, 14/

Sural nerve, 515, 516/, 5 1 6r

Surface anatomy, 2 of body's muscles, 330/,

332/ Surface tension,

Superficial (external)

orientation or direction, Superficial fascia (hypodermis),

848

of water molecules,

Surfactant,

13t

36

848-849

Surgical neck (humerus), 232/,

233

Superficial reflexes,

526

Superficial space, muscles

of,

350t, 351/

Superior (cranial) orientation/direction,

1

3t

Supination (movement), 262, 263/, 362-363r, 363/ Supinator muscle, 358f, 359/, 360t, 361/

summary

235/ Supraspinous ligament, 220/, 471/ Suprasternal (jugular) notch,

plasma/IF/ICF, 1036/

152 538/

by, 355r Suprascapular notch, 230/,

Supraspinatus muscle, 353/, 354, 355r, 356/ actions of (summary), 362-363r, 363/ Supraspinous fossa, 230/, 232,

Sulci,

Sulfate, in

Suprarenal veins, 764/, 764f, 765/ Suprascapular nerve, 512r,

232

46

simple, 44, 45/. See also

of spinal cord,

Suprarenal arteries, 746/, 752/, 754f, 755/ Suprarenal glands. See Adrenal glands

513/ muscles served

blood. See Blood glucose

Subclavian arteries, 679/, 746f,

Subluxation, 272

stretch

Striate cortex.

Subarachnoid space, 434, 464, 465/, 472/

890-891, 891/

629-630, 630/

Sudden infant death syndrome (SIDS), 876

double (disaccharides), 44,

Sublingual gland, 504r, 882/,

glands and, 626f,

Striae,

Sudoriferous (sweat) glands,

vessel wall, 712, 713/

Stress response, adrenal

927 46

of,

44, 45/,

506/ Subacromial bursa, 257/, 269/ Subacute hypersensitivies, 821 Subarachnoid hemorrhage,

Subendothelial layer of blood

313

Suprapatellar bursa, 267/

Suction lipectomy, 991

467

Supraoptic nuclei, 446/, 447, 612, 612/ Supraorbital foramina

205/

Sucrose chemical digestion of,

femur,

lines,

241/ Supracondylar ridge, humerus, 232/ Suprahyoid muscles, 340, 340-341r, 341/

Supraorbital margins, 204,

927

synthesis

Supracondylar

217f

Stylomastoid foramen, 207, 208/, 217?, 504f Stylopharyngeus muscle, 505r,

Subcostal nerve,

Stress (mechanical), bone's

response

ulna, 233, 234/

Supraclavicular nerves, 510/, 51 It

(notches), 204, 205/, 214/,

Subthalamic nuclei, 443 Sucking reflex, 932 Sucrase,

556/ Suppressor factors, 8 1 4t Suppressor T cells, 808/, 813f Suprachiasmatic nucleus, 446/,

635-636

of,

Substrate-level phosphorylation,

Straight sinus, 464/, 465/,

of taste buds, 555,

447, 459, 579/, 580,

of actions

Stylohyoid ligaments, 216

341/

559

750;

Subscapular bursa, 269/ Subscapular fossa, 230/, 232, 235/ Subscapularis muscle, 353/,

summary

140, 140/

cells,

of equilibrium, 592, 593/

trafficking, 78, 79, 79/ Substantia nigra, 443, 449,

Styloglossus muscle, 339/,

339f

Stopcodon, 110, 111/

stomach, 900/ tracheal, 837, 837/

of actions

362-363t, 363/

of,

Suspension mixtures, 32 Suspensory ligament breast, 1086, 1086/ of eyeball, 565, 565/, 569/ of ovary, 1079, 1080/, 1082/ of penis, 1065/ Sustentacular cells (Sertoli cells),

1074

Sustentaculum

tali,

243

Sutural bones, 205/, 211

2

2

1237

Index

Sutures, 203, 205/, 206/ as fibrous joints, 253, 253/,

T4

253

Synarthroses,

621/

256;, 258; See Stroke volume Swallowing (deglutition), 883, 883/, 896-897, 897/, 911;

258?, 259; Synchondroses, 254-255, 254/

340-34 If Sweat, 157-158 Sweating, 989

Syncope, 458 Syncytiotrophoblast, 1115,

Sweat (sudoriferous) glands, 157-158, 157/, 545f Sweet taste sensation,

Syncytium, 284 Syndesmoses, 253-254, 253/

SV.

muscles

of,

structure/functions, 256;,

258f

Sympathectomy, 550 Sympathetic chain (paravertebral) ganglia,

509/, 538/, 539/ Sympathetic division of ANS, 388-389, 534 anatomy, 537-541, 538/ heart and, 693, 693/ kidneys and, 546, 1008/,

1009-1010 546 metabolic effects, 546 parasympathetic division vs., 534, 535/, 535f physiology drugs that influence, 542- 543, 544; interactions with parasympathetics, 543- 546, 545; neurotransmitters,

541-542, 543; thermoregulatory responses

545-546 of, 544-545

to heat,

unique roles Sympathetic trunks, 537, 538/, 539/ Sympathetic (vasomotor) tone,

544 Sympatholytic agents, 544f

Sympathomimetic

agents,

544t

Symphyses, 254/, 255, 256f, 258f, 259t

Symport

pump

system, 77,

77/ Synapses, 408/, 409-415, 409/ chemical, 409-410, 411/ electrical,

409, 409/

Synapses en passant, 518 cleft,

289/, 290, 292/,

410 in smooth muscle, 310 Synaptic delay, 410 Synaptic knobs, 393. See also

Axonal terminals Synaptic potentiation,

Template,

Synaptotagmin, 410

fluid, 255/,

256, 257/

in,

1

4/

Tarsometatarsal joints, 259;

243

Tarsus,

Tastant, 557

Taste buds, 555, 556/ Taste (gustatory) cells, 555,

556/ by,

260-262/

Taste pore, 555, 556/ Taste sense, 555-558, 556/ activation of taste receptors,

structure/functions,

255-256, 256f, 258-259t types of, 264-266, 264-265/ 255/,

256, 257/ joint,

259;

561, 561/

257, 259

membrane,

of,

summary, 246; Tarsal (Meibomian) glands,

258-259;, 259-264,

557, 557/ aging and, 596

555-557

basic sensations,

cortical area, 437/, 440,

557/

developmental aspects, 596 influence of other senses on,

558

271/

Synovitis, 275,

276

Synthesis reactions, 38, 38/. See also Dehydration synthesis

transduction mechanism,

557 Tata box, 106, 107/ Tattoos,

1096

163b

Tau, 468

Systemic anatomy, 2 Systemic circuit, 682-683, 682/ Systemic circulation, 745/, 745; major pathways, 740 arteries, 746-757, 747/

Tay-Sachs disease, 90, 1145

758-766, 759/ monitoring efficiency of, 729-731, 731/ overview, 745/, 745; Systemic lupus erythematosus

T cells

veins,

(SLE), 819,

TBGs

(thyroxine-binding

621

globulins),

TB (tuberculosis), 870 T cell-dependent antigens, 813

T cell-independent

815

delta,

suppressor, 813;,

(triiodothyronine),

619-622, 620;, 621/

811-814,

response,

Tl (monoiodotyrosine), 620- 621, 621/

T3

798-801, 809-812 killer, 808, 808/, 811-815, 813;

816

thymic hormones and, 636

562 mechanism,

Tears (lacrimal secretions), as protective

793; Tectorial

103/

DNA,

99, 100/

Template strand, 106, 107/ Temporal arteries, 748/, 748;, 749/ pulse rate and, 731/ Temporal bones, 205/, 206/, 207, 208/, 209/ articulations of, 258; fetal, 247/

summary, 217; Temporalis muscle, 331/, 337/, 338, 338;, 339/ 503; Temporal line, 339/ Temporal lobe of cerebral hemispheres, 435/, 436, 437/, 445/, 447/

Temporal nerve, 504-505; Temporal summation, 412, 413/ Temporal veins, 760/, 760;, 761/ Temporomandibular joint, 207, 212, 212/, 258; Tendinous intersection, of rectus abdominis muscle, 349/ Tendonitis,

273

Tendons, 134/, 491, 492;. See

under muscles

specific

of shoulder joint,

813; in

621- 622, 621/

Telophase, of mitosis, 101,

257/

816

helper, 808, 808/,

immune

1 1

Telomeres, 112

Tendon sheaths, 256-257,

775, 775/

gamma

1 1

Telomere clock,

also

(T lymphocytes), 657,

cytolytic,

824

(diiodotyrosine), 620,

antigens,

813

697/ Systolic blood pressure, 723, 723/

Systole, 696,

T2

163

cycle,

Tarsal region,

255,

491, 492;

413-414 Synaptic vesicles, 290, 410

Telogcn phase, in hair growth

Tarsal plates, 561, 561/

articulations 22/',

movements allowed

Synapsis, 1071

Synaptic

393

"Tailor's muscle", 367;

Temperature body. See Body temperature influencing chemical reactions, 40 receptors for, 490-491, 492f Temperature receptors, 475/

general sensory receptors

Syphilis,

branches), neuron, 392/,

491

Tarsal bones, 229/, 243, 245/

Synovial joints, 255-271, 255/ factors influencing stability

elbow

491

325

255/ elbow joint, 271/ of hip joint, 270/ of knee joint, 267/

Synovial

894

hormones, 610

Synovial cavity, 22,

receptors, 541-542, 543;

disease,

Telencephalon, 432/ Telodendria (terminal

Telomerase,

Synostoses, 253

of,

893-894, 893/

gum

Ankle Target cells of hormones, 605 interaction of hormones at, 610 specificity of, 609

Synergist muscles,

Synovial

localized vs. diffuse effects,

of

of,

tooth and

also

1059

617;,

as accessory digestive organ,

883

Talus, 243, 245/, 246;. See

of inappropriate

Synergism

Tectum, 449, 449/ Teeth, 892-894, 892/

structure

702

Tactile corpuscles,

ADH secretion (SIADH),

response, 789, 790/

807-808,

cells),

808/ Tabes dorsalis, 526

Tactile (Merkel) discs, 152,

structure/functions, 256;,

Syndrome

(CD4

cells

Tachykinins, 417;

259;

Swelling, in inflammatory

T4

Tachycardia,

1115/, 1116/

555-557

619-622, 620;,

(thyroxine),

structure/functions, 256/,

membrane,

590 479

586/,

Tectospinal tracts, 477;,

269/

Teniae coli, 921/ Tennis elbow, 384

Tension lines in skin, 155-156 Tensor fasciae latae muscle, 331/, 367, 368/, 370f,

379; Tensor tympani muscle, 584, 584/ Tensor veli palatini muscle, 341/ Tentorium cerebelli, 463/, 464, 464/, 465/ Teratogens, 1129, 1129/

,

1238

Index

Teres major muscle, 333/,

354, 356/ actions of (summary),

362-363t 363/ Teres minor muscle, 353/, 354, 355r, 356/ ;

actions of (summary),

362-363t, 363/ Terminal arteriole, 719, 719/ Terminal branches (telodendria), 392/,

393

Terminal bronchioles, 839, 839/ Terminal cisternae, 287, 287/ Terminal ganglia, 535 Terminal hair, 160 Termination signal, 106, 107/ Testes, 604/, 634, 1064, 1064/, 1065-1067, 1065/, 1066/

1066 cancer, 1067 fluid, 1076

Testicular arteries, Testicular Testicular

Testicular veins, 764/, 764f 765/, 1065/,

1066

Testosterone, 629, 634, 651,

1066, 1078, 1078/ anabolic steroids and, 308b 1 60 on metabolism,

hair growth and,

influences

977f of,

626f, 1079,

1095t

320

fused/unfused, 297/,

298

624 Tetrads, 1071

Tetany,

Tetralogy of Fallot, 706, 707/

TF

muscles, 331/, 352-353:,

(tissue factor),

innervation

66 If, 662,

of,

514/, 51 4t,

515 muscles acting on, 367-372r, 368/, 372/ actions of (summary), 379-380t, 380/ veins, 759/, 766/, 766t

Thin

282t, 284, 285/ in cardiac/skeletal/smooth

muscles, 3 1 5t

Thin

skin, 153, 154/

Third-class levers, 328, 329/,

330 Third-degree burns, 168, 168/ Third-order neurons, 474,

445,

750f,

751/',

Thoracic cage (bony thorax), 226-228, 227/ Thoracic cavity, 15, 17/ anatomical relationships of organs in, 676, 677/, 842/ pressure relationships

454 embryonic development, 431, 432/, 433 main nuclei of, 446/ as limbic structure,

Thalassemias, 653 Thalidomide, 819-820, 1129 Theca folliculi, 1081/, 1089, 1090/ Thenar eminence, 364t Thenar muscles, 359/ Theory, cell, 64 Thermogenesis, chemical (nonshivering),

987

Thermoreceptors, 490, 492t Thermoregulation hypothalamus' role in, 987 skin and, 171b sympathetic, 545-546

Thermoregulatory centers, 987 Theta waves, 456, 457/ Thiamine (vitamin Bl), 948f Thick (myosin) filaments, 282/, 282r, 284-286, 285/, 286/ Thick skin, 153

phenomenon

Thrombophlebitis, 741 Thrombopoietin, 660

Thymic Thymic

Thoracic curvature, 219-220, 219/ Thoracic duct, 773, 774/ Thoracic nerve, 512r, 513/ muscles served by, 352r Thoracic region, 14/ Thoracic spinal nerves, 470/, 508/ Thoracic vertebrae, 219, 219/ articulated, 224/ as part of axial skeleton,

204/ regional characteristics,

224-225

Thoracolumbar division

268 ligaments

of,

266

379-380f, 380/

636

superficial view, 330,

779, 779/ 56/, 99,

100/

Tibial tuberosity, 242/, 243, Tibial veins, 759/, 766/, 766t

Thymus

Tibiofemoral (knee) joint

244/

gland, 604/, 636,

777/, 779, 779/

749f Thyroglobulin, 619, 620,

Tibiofibular joints, 242/, 243,

621/ Thyrohyoid membrane, 341/, 834/ Thyrohyoid muscle, 339/ 341/, 341t Thyroid arteries, 618, 748/, 748/, 749/ Thyroid cartilage, 339/, 341/, 832/, 834, 834/ Thyroid gland, 604/, 618-623, 619/, 832/ Thyroid hormone (TH), 619 major effects on body, 620f regulation,

transport,

621-622

244/, 259£

Tic douloureux, 503f

volume (TV), 849, 850/ Tight junctions, 68, 69/ of blood-brain barrier, Tidal

466-467 of continuous capillaries,

718, 718/ of epithelial cells,

118

Tin, 28t

Tine

test,

Tinnitus,

822 592

Tip-links, 590, 590/

Tissue factor (TF), 66 It, 662,

621-622

663/ Tissue perfusion, 732-740

Thyroid-stimulating hormone (TSH), 615, 616f, 622

Thyroid storm (thyroid

articulations of, 259r replacements for, 194b, 195/, 274t

crisis),

640

autoregulation,

733-734

blood flow at rest/during exercise, 732,

732/

Sympathetic division of

Thyroid veins, 760/, 761/ Thyrotrope cells, 615

735 in heart, 736 in lungs, 735-736

ANS

Thyrotropin-releasing

in skeletal muscles,

ANS, 537. See

of

also

Thorax arteries, 746/', 747/,

749/-751/, 750t, 75 It innervation of, 510, 540, 540f

331/

tendon, 377/, 378/, 382/ Tibial nerve, 515, 516/, 5 1 6r muscles served by, 376f

Thymopoietins, 636 Thymosins, 636

synthesis, 620-621, 621/

Thoracoacromial arteries, 750/, 750t Thoracodorsal nerve, 513/ muscles served by, 354r

243, 244/ knee joint and, 266, 267/,

crest, 242/,

actions of (summary),

'

846/

condyles, 242/, 243, 244/

756f, 757/

237

55-57,

244/

259f

pulse rate and, 731/ Tibialis muscles, 373t, 374/, 375/, 376t, 378/

(Hassall's) corpuscles,

(T),

of,

Tibial arteries, 747/, 756/,

Thyrocervical trunks, 749/,

expiration, 846-847,

'

364f, 365/

factor,

Thymine

articulations

662

TH. See Thyroid hormone Thumb, 14/ of,

467-468

Tibia, 229/, 242/, 243,

muscles acting on, 367-372: summary, 246r

agents, 717/7

(pollex), 14/,

body, 620f

621/ TIAs (transient ischemic of,

attacks),

48f,

on

effects

synthesis

Thromboembolytic disorders, 665 Thrombokinase, 66 It Thrombolytic (clot-dissolving)

in,

during inspiration/

ascending spinal cord tracts

major

Threshold stimulus, 298, 298/ Thrombin, 663, 663/ Thrombocytopenia, 666

muscles

75 It

on metabolism, 977t in heat-promoting thermoregulation, 987

and, 405

Thumb

445/, 448/, 449/

and, 475/

all-or-none

Thirst mechanism, arteries, 749/, 750/,

985 influences

580 Threonine, 945/ Threshold, 402, 403/

Thromboxanes, Thrombus, 665

1037-1038, 1038/

347/

Thyroxine-binding globulins (TBGs), 621 Thyroxine (T4), 619-622 basal metabolic rate and,

762-763f, 763/ Thoroughfare channel, 7 1 5/, 719, 719/ Three-dimensional vision,

475/ Third ventricle of brain, 432/, 434, 434/, 442/, 444/, 445/, 449/ CSF and, 465/ Thirst center, 447, 1037

844-845, 845/ 442/', 444/',

of breathing, 346f,

veins, 758/, 759/, 762/,

(actin) filaments, 282/,

663/

Thalamus,

353/

756-757/, 756-757( bone (femur), 241-242, 241/, 244/, 246/

Thoracic

mechanism Tetanus,

Thigh arteries, 746/, 747/,

353/',

in brain,

hormone (TRH), 615, 616t,

734-735

622

in skin, 735

Thyrotropin (thyroidstimulating

hormone

TSH), 615, 616f, 622

or

velocity of, 733, 733/ Tissue plasminogen activator

(TPA), 664, 717b

0

1

1239

Index

Tissues, 3, 4/, 117-150, 118 cardiac muscle, 140, 141/,

280 connective, 126-138 142,

blood, 138

135-137

cartilage,

characteristics

783 777/ 779, 782, 831/, 832/, 833 Torticollis, 384 Total dead space, 851

Transport proteins, 52f, 67, 67/, 72/ Transport vesicles, 87/, 88, 88/,

Total lung capacity (TLC), 850,

Transverse arch of

Tonsillitis,

Tonsils, 556/,

850/ Total metabolic rate (TMR),

of,

126-130 130-135 osseous, 137-138 covering and lining membranes, 138-140 developmental aspects 144, 147 epithelial,

118-126

repair

of,

44

287

in elastic filaments, 284,

285/ lung capacity), 850, 850/ (total

TLRs

T

Transverse fracture, 191 Transverse/horizontal plane

plasminogen activator), 664, 717b

(cross section), 15, 16/

Trachea, 829, 830/, 832/,

Transverse ligament of palm,

269/

(toll-like receptors),

359/

789,

(summary), 836f muscles near, 341/ wall tissue, 837, 837/

838 Tracheoesophageal fistula, 932 Tracheotomy, 876 Trachoma, 598 Traction, 199 Trachealis muscle, 837/,

392

Transverse lines, 225, 225/ Transverse process, 219/, 220/,

236/ 330/',

33 If,

813t, 814-815, 815/

suppressor, 813/, 816 thymic hormones and, 636

TMR (total metabolic rate), 985 Toes (phalanges), 229/, 245, 245/ articulations of, 259t hallux (great toe), 245 innervation of, 515, 51 6/, 516f muscles acting on, 373-378f actions of (summary),

379-380r muscles of (intrinsic), 381-383f Toll-like receptors (TLRs), 789,

791 Tongue, 832/, 882/, 888/, 889-890, 889/

taste,

557

108 Transforming growth factor, 814f Transfusions (blood), 667-670 initiator,

670 exchange, 669 autologous,

packed red reactions

to,

whole blood,

Transient ischemic attacks (TIAs),

467-468

Transitional epithelium,

123-124, 124/ Transitional period of infants,

1134 movements, 260, 264

as accessory digestive organ,

Translation (genetic), 105,

883 muscles

Transmembrane

extrinsic,

507t,

106/,

338, 339/, 339f,

889

338, 507f, 889 taste buds, 555-557, 556/ Tonicity, 74-75, 75/ osmolarity vs., 74 Tonic receptors, 496 intrinsic,

Trapezoid bone, 23

If, 236, 236/ Treppe, 298-299, 299/

(thyrotropin-releasing

Triads,

108-110,

109/, 111/'

proteins, 67,

67/, 69, 72, 72/,

73

immune 818

pancreatic

islet cells,

634b

Tropomyosin, 286,

292/

286/',

362-363f, 363/ tendon, 271/ Triceps surae muscles, 376f, Trichosiderin, 160

Tricuspid valve, 680/, 681/,

684, 685/ Trigeminal ganglia, 503f Trigeminal nerves (V), 448/, 450, 450/, 499, 500/, 503f muscles served by, 338,

536 Trigeminal neuralgia, 503f Trigger zone of motor neurons, 393, 396f Triglycerides, 46-47, 47/

of,

967-968,

1

330-331/,

332-333/ Trunks, of brachial plexus,

511, 512f, 513/ Trypsin, 917-918, 918/, 926/,

928, 928/ Trypsinogen, 917, 918/ Tryptophan, 945/

TSH

(thyroid-stimulating

hormone!, 615, 616f, 622 t-SNAREs, 78, 78/ T (thymine), 99, 100/ T tubules, 287/', 288, 289/ in cardiac/skeletal/smooth

muscle, 314t Tubal ligation, 1125b Tubal tonsils, 782, 831/', 833 Tuber calcanei, 243, 382/ Tubercle (bone marking), 179f Tubercle of the iliac crest, 237,

238/ Tuberculosis (TB), 870

Tuberculum

location/function in body,

5

345/, 348f, 349/ superficial,

actions of (summary),

metabolism 967/

of,

muscles, 342-344f, 343/,

332/, 333/, 356/, 357f,

48f

kidney, 1021b

448,

234/, 235/

359/

973

rejection and, 816,

233

448/, 449/, 499, 500/,

innervation

Triceps brachii muscle, 331/,

in absorptive state, 972/,

Transplantation

(IV),

Trunk

287/ 288

parasympathetic fibers and, 260/,

232/',

True capillaries, 719, 719/ True (frank) baldness, 164 True pelvis, 239, 239 True ribs, 226-228, 227/, 228/ True solutions, 3 True vocal cords (vocal folds), 832/, 834/, 835, 835/ Truncus arteriosus, 703

338t, 340r

Translational (gliding)

humerus,

Trochlear nerve

353/ accessory nerve and, 507f

380/

668 669-670 668

cells,

of

271/ 563/

joint,

Troponin, 286, 286/, 315f

Triglycerides

88/ Transferrin, 652, 652/', 931 Transfer RNA (tRNA), 105 face, 88,

elbow

332/, 333/', 337/, 352f,

hormone), 615, 616f, 622 Triacylglycerols. See

Trans

108 Trochanter (bone marking), 179f Trochlea

Tropins (tropic hormones), 613

Trapezius muscle,

TRH

808, 808/, 811, 811/,

RNA), 105

(transfer

initiator,

Trochlear nuclei, 449 Trophoblast cells, 1114,1114/

Transducin, 577, 578/ Transduction, 493

798-801, 809-812

tRNA

muscle, 331/, 348f, 349/ Trapezium bone, 23 If, 236,

812, 812/, 813f in immune response, killer,

94

Triquetral bone, 231/, 236,

502f, 564 Trochlear notch, ulna, 233,

Transcytosis, 78, 79, 79/

105-108, 106/, 107/

Triplets (genetic), 105, 111/

221, 221/, 222f Transverse sinuses, 463/, 760/, 760f, 761/ Transversus abdominis

Tracts,

Transcription (genetic),

Trimethaphan camsylate, 544f Tripeptides, 49

eye, 563,

791 lymphocytes (T cells), 657, 775, 775/ cytolytic, 815 gamma delta, 816 helper, 808, 808/, 811-814,

Transamination, 969, 969/ 970t

of,

236/

Transverse humeral ligament,

cartilages, 177/, 834/', 837,

on body, 620f 621/

effects

synthesis

223/

Trabeculae carneae, 681, 681/ Trace minerals, 953-954t

features/functions

662, 663/

TLC

TPA

837/

Tissue thromboplastin, 66 lr, Titin,

Transverse foramen, 222/, 223,

(tissue

619-622

Triplets (microtubule), 92,

Touch, receptors for, 475/, 490-491, 492f

142-144

142, 144

scar,

245,

435/

837-838 of, 1

foot,

247

Transverse cerebral fissure,

Trabeculae, 179, 184/

of,

muscle, 140-142 nervous, 140 regenerative capacity

Transpulmonary pressure, 845

985

connective tissue proper,

Triiodothyronine (T3),

major

91/

245/,

Trigone, 1023, 1024/

sellae, 208/',

209

Tuberosity (bone marking),

179f Tubular exocrine glands, 125-126, 125/

1240

Index

Ulna, 229/, 23 If, 233, 234/, 235/

Tubular reabsorption,

1010-1013, 1010/ passive, 1012 Tubular secretion, 1014

of, 258/ elbow joint and, 271, 271/ muscles acting on, 356/,

357t

126 Tubuloglomerular mechanism, 125/',

of renal autoregulation,

1007-1009, 1008/ Tubulus rectus, 1065, 1065/, 1066/

Tumor

necrosis factors (TNFs),

814r Tumor suppressor genes (antioncogenes),

145b

362-363f, 363/

Ulnar arteries, 747/, 750/, 750f Ulnar nerve, 512, 51 2f, 513/ muscles served by, 358f, 359t, 364t, 366f Ulnar notch, 234, 234/ Ulnar veins, 759/, 762/, 762f, 763/ Ultrasonography, 206, 1135

adventitial, 712, 713/ Tunica interna (tunica intima), 712, 713/ Tunica media, 712, 713/ Tunica vaginalis, 1065, 1065/, 1066/, 1101, 1101/ Tunics blood vessel, 712-713

Umami

564-568

of alimentary canal,

Ultrasound therapy, fracture sites,

1

for

946

taste sensation,

555-556 arteries, 740, 1126, 1127/ Umbilical ligaments, 1134 Umbilical region, 14/, 18, 19/ Umbilical veins, 740, 1126, 1127/ Uncinate fits, 560 Uncus, 437/, 440 (after

polarization),

hyper-

404

Nasal conchae Turbulent blood flow, 722 Turner's syndrome, 1098 TV (tidal volume), 849, 850/ T wave, 694, 694/

Unfused (incomplete) tetanus, 297/, 298 Uniaxial movement, 260

Two-neuron chain, 532

Unipennate fascicle pattern, 326, 327/

497 Tympanic

discrimination

test,

cavity (middle ear),

perforated,

591-592

secondary, 582

Tympanic

Unicellular exocrine glands, 124, 125

Unipolar neurons, 395,

582-584, 583/ bones of, 583-584, 583/, 584/ Tympanic membrane (eardrum), 582, 583/, 584/

region, of temporal

bone, 207, 209/

Type A daughter cell, 1074 Type B daughter cell, 1074 Type la fibers, 522, 522/, 523/ Type I cells, 840, 841/ Type I diabetes mellitus, 6346,

396-397f Universal donor,

Type

Type Type

I

Universal solvent, 40, 1034 Unmyelinated nerve fibers,

394, 407 Unsaturated fats, 47 Upper limbs arteries, 746/, 747/,

750-751/, 750-75 It bones, 23 It,

innervation

233-237 of,

510-513,

759/

hypersensitivities,

762/,

diabetes mellitus,

Up-regulation of receptors,

609 Uracil (U), 55-57, 56/

Urea, 1-22, 969, 969/ 1012,

634-6356

1017

Type

II fibers, 522, 522/ Tyrosine (phenylalanine), 415/,

in blood plasma, 647f

Urea

cycle,

969, 969/

Urease, 901

608, 945/

Ureteric buds, 1027, 1028/

Ubiquitin, 110 Ulcer, decubitus,

172

Ulcers

duodenal, 910 esophageal, 896 peptic,

936

Ureteric ducts, 1027, 1028/ Ureters, 997/, 999/, 1003/,

1023, 1023t, 1024/ ANS fibers, 536/ Urethra, 997/, 1025

1024/ 1025,

and volume, 1014-1018 1022 Urobilinogen, 652, 916 Urochrome, 1022

1080/ Urethral sphincter

specific gravity of,

1025 1024/ 1025 Urethritis, 1025, 1096 Uric acid, 1012, 1022 external, 1024/, internal,

Urogenital diaphragm, 350t,

351/ 1024/ 1025, 1064/ Urogenital ridges, 1027, 1028/ Urogenital sinus, 1027, 1028/

in blood plasma, 647t

Urinalysis,

1029

Urinary bladder, 997/, 1023-1024, 1064/

ANS

fibers/effects,

Urologist,

535/

551 1029

1092-1094, 1093/ Uterine tubes, 1079, 1080-1083, 1080/ 1082/

developmental aspects,

1027-1028 position,

Uterosacral ligament, 1080/,

when

1082/ 1083

distended/empty, 1025/ structure

of,

1029

Uterine arteries, 1084, 1084/ Uterine glands, 1083, 1084/ Uterine (menstrual) cycle,

536/, 538/, 545t atonic,

pH

and transparency, 1022 1022 of, 1022

regulation of concentration

1064/, 1068/, 1069/,

Uterus, 1079, 1080/ 1082/

1083

1024/

transitional epithelium

of,

123-124, 124/ Urinary retention, 1027 Urinary system, 7/ 996-1032, 997, 997/ See also under Renal acid-base balance and, 1050-1053, 1051/

anteverted, 1083

prolapsed,

1083 1083

retroverted,

sympathetic nerve 538/

fibers,

1083-1084, 1084/ 585/ 593/ 594/ Utrophin, 319 wall

of,

Utricle, 584,

aging and, 1029

Uvea

cardiovascular system and,

564-567, 565/ Uvula, 831/ 832/ 833, 888/

742b, 743b developmental aspects, 1027-1029, 1028/ digestive system and, 934b disorders, 1020-10216, 1023, 1025, 1027 during pregnancy, 1131 endocrine system and, 638b integumentary system and, 1706 interrelationships with other systems, 10566, 10576 kidneys, 997-1022. See also Kidneys lymphatic system/immunity and, 7806

512t, 513/ veins, 758/,

762t, 763/

820-821, 821/ II cells, 840, 841/ II

670

Universal recipients, 670

819

color odor,

orifice,

mechanism,

793f chemical composition, 1022

Urethral groove, 1098

cancer,

Umbilical

Undershoot

886-887, 886/ Turbinates, 211. See also

Two -point

1069

as protective

Urethral folds, 1098

Urethral

actions of (summary),

Tunica albuginea, 1065, 1065/, 1066/, 1068/, 1080, 1081/ Tunica externa (tunica

eyeball,

fibers/effects, 545t male, 1064, 1064/, 1068/

articulations

Tubulins, 91, 92/ Tubuloalveolar exocrine glands,

ANS

micturition,

1025-1027

muscular system and, 3166 nervous system and, 5486, 1026/ reproductive system and, 11036 respiratory system and, 8746 skeletal system and, 1976 urinary tract organs,

1023-1025 Urination (voiding),

1025-1027, 1026/ Urine, 1006

abnormal constituents, 1022f

(vascular tunic),

889 Vaccines, 802-803, 803/

Vacuum-assisted closure (VAC), 148

700 537 Vagina, 1079, 1080/ 1082/ 1084-1085 ANS effects/fibers, 535/ 536/ 538/ 545t Vagal tone,

Vagal trunks,

Vaginal fornix, 1085, 1085/ Vaginal orifice, 1085, 1085/ Vagotomy, 551 Vagus nerves (X), 448/ 449/ 451, 451/ 500, 500/

food intake and, 982-983 gustatory pathway, 557,

557/ heart innervation and, 693,

693/ implanted stimulator to treat epilepsy,

muscles served

by,

457 34 It

origin/course/functions, 506f

parasympathetic fibers, 536-537, 536/ Valence shell, 33, 33/ Valine,

945/

Vallate papillae, 555, 556/,

889, 890/

1

1

1241

Index

Valsalva maneuver, 348t, 836,

925 Valvular stenosis,

686-687

Vaporization, of water, 40

number tandem (VNTR), 95b

Variable (V) region, 804, 804/

720-721 Varicosities, 310, 311/, 518 Variocele, 1077 Varicose veins,

Vasa recta, 1002, 1003/ Vasa vasorum, 712 Vascular anastomoses, 721 Vascular endothelial growth factor (VEGF), 194b Vascular shock,

738-740

Vascular shunt (metarteriole-

thoroughfare channel), 719, 719/' Vascular spasm,

661-662

Vascular system, 740. See also

Blood vessels

564-567, 565/

Vas (ductus) deferens, 1064, 1064/, 1065/, 1066/,

1067-1069

4/

160

areas drained, 758-759/,

blood flow velocity in, 733/ blood pressure in, 723-724, 723/ inferior, 678, 679/-682/, 758;, 764;, 765/ superior, 678, 679/-682/,

control of

ANS

functioning,

547 Vasomotor fibers, 544, 725, 727/ in blood vessel walls, 712 Vasomotor tone, 544, 725 Vasopressin (antidiuretic hormone), 61 It, 618 Vastus muscles, 368/, 369f, 370t, 379t, 380/

331/ VC (vital capacity), 850, 850/ Vegetarian diets, 945/ superficial view, 330/,

VEGF

(vascular endothelial

growth

194b Veins, 712, 720-721 arteries vs., 740 factor),

blood flow velocity in, 733/ blood pressure in, 723-724,

772, 773/ major, of systemic circulation, 758/,

758-759f, 759/ of

pulmonary

circulation,

221-226, 222t

889

vaginal, 1085, 1085/

Vestibulocochlear nerve

vertebra structure, 221, 221/ Vertebral foramen, 221, 221/, 222/, 222;

(VIII),

448/, 449/, 451, 500, 500/, 585, 591/

origin/course/function, 505;

Vibration receptors, 490, 492f

Vertebral (spinal) cavity, 15,

Vibnssae (nasal hairs), 830 Villi, 908-909, 909/, 910/

Ventilation

Vertebra prominens (C7), 223,

Viral load,

224/ Vertebrochondral 227/

Virilization of females, 626;

minute, 851 pulmonary, 829. See also Breathing

855-856, 855/

17/ Vertebral veins, 760/, 760;,

761/

Ventral (anterior) horns, 471, 472/, 473/

1

muscles served 367f

by, 344;,

Ventral roots, 471, 472/, 473/,

508, 539/ rootlets, 508, 509/

ribs,

cerebral, 432/,

433-434,

434/ heart, 678, 679/, 680/, 681, 681/, 682, 682/, 683/ embryonic, 703, 703/

227/

Ventricular tachycardia

(VT or

708

78

Vesicles,

brain, 431, 432f,

in,

723/

Vermiform appendix,

777/,

782, 882/, 921, 921/ Vermis, 453, 453/ Vernix caseosa, 1 69

219

synaptic, 290,

410

transport, 87/, 88, 88/, 91/

Vesicouterine pouch, 1080/,

1083

Vertebral arch, 221, 221/, 470/ Vertebral arteries, 746/, 747/, 748/, 748;, 749/

body (centrum), 221,

221/-224/, 222f

258f Vertebral canal, 221, 221/ of,

Visceral association area,

pericardium (epicardium), 676, 677/ Visceral motor system. See Autonomic nervous

system motor zones, 473, 473/, 537, 539/

Visceral muscle, 313. See also

Smooth muscle innervation

of,

518 906

plasticity of, 904,

Visceral organs (viscera), 15, 17/

Visceral pain,

494b

Visceral pericardium, 18, 18/, 139/, 676, 677/, 681/'

Visceral peritoneum, 18,1

Vesicular follicle (Graafian

1080, 1081/,

139/,

8/,

885-886, 885/, 887

Visceral pleura, 18, 18/, 842/,

139/',

844

Vesicular (substance)

Visceral reflex arcs, 541, 541/

traffkkmg, 78, 79, 79/ Vesicular transport, 77-80,

Visceral reflexes, 541, 541/ Visceral sensory neurons, 541,

541/

81-82r

Visceral sensory zone of spinal

1069

592 440

Vestibular apparatus, Vestibular cortex,

Vestibular division, of

gray matter, 473, 473/ Visceral serosa, 17-18, 18/,

139-140, 139/

vestibulocochlear nerve,

Visceral vs. somatic afferent

505f

nerve fibers, 388, 389/ Viscera (visceral organs), 15,

Vistibular folds (false vocal cords), 832/, 834/, 835,

835/

204/

articulations

433

caveolin-coated, 80, 80/, 82t clathrin-coated, 79, 79/, 8 If

Vesiculase,

Venules, 712, 714;, 720 blood flow velocity in, 733/

497 441 nerves, 497

Visceral afferent nerves,

Visceral

1089-1090

blood pressure

1133

Perpendicular plate Very low density lipoproteins (VLDLs), 977-979, 979/',

follicle),

707/

Viscera, abdominal, muscles

Visceral layer of serous

(childbirth), 1132/,

696, 697/ Ventricular muscle, 691/ Ventricular septal defects, 706,

intestinal

819

Visceral efferent

Ventricular ejection phase,

Vertebral

226-227,

coatomer-coated, 80, 82t, 87/ secretory, 78/, 88-89, 88/

Ventricles

VIP (vasoactive

that compress, 347/, 348;

Vertebrocostal joint, 25 8f

982

(VRG), 861-862, 862/

Vertebrae,

227,

Vertical plate. See

3r

Ventral respiratory group

V-tac),

ribs,

Vertex presentation

Ventral (anterior) orientation

1077b

peptide), 904, 905;

Vertebrosternal

structure, 221, 221/

to,

of oral cavity, 888/,

regional characteristics,

Viagra,

compared

lymphatic vessels in relation

of nasal cavity, 830, 832/.

Vertebral ribs, 227, 227/

as part of axial skeleton,

vessels, 7 14t

343/, 345/

1096-1097 Venous anastomoses, 721 Venous return, 699 Venous sinuses, 721 Venous valves, 713/, 720

723/ blood transport and, 645 to other blood

of ear, 505f, 583/, 584, 585/

Vestibulospinal tracts, 477;

Ventral rami, 508-509, 509/

inflammatory response, 789, 790/, 791 Vasomotion, 736-738, 736/ Vasomotor center, 45 blood pressure and, 725-726, 727/

583/, 585/, 586/

Vestibule

Vertebral region, 14/

Ventral body cavity, 15, 17/

in

594

Vestibular (oval) window, 582,

Vertebral pedicles, 221, 221/

Vasectomy, 1068-1069, 1125b 904, 905f

muscles, head/trunk

Vestibular nystagmus,

758;, 759/-763Z Venereal diseases (VDs),

Vasoactive intestinal peptide (VIP),

(spine),

219-226, 219/ curvatures, 219-220, 219/ divisions, 219, 219/

movements, 342-344t,

or direction,

Vasoconstriction, 712, 727/ Vasodilation, 712, 727/

column

Vertebral 1

Ventilation-perfusion coupling,

Vascular tunic (uvea) of eyeball,

7 3f, 7

758-759;

Variable, 9-10, 9/

repeat

Vellus hair,

744-745; of,

Venae cavae

Vanadium, 28r

Variable

744/,

structure

Vestibular ganglia, 505f, 585/,

593, 593/, 594/ Vestibular glands, greater,

1085 Vestibular

17/ Visceroceptors (interoceptors),

491, 492t Viscosity, blood, 648, 654,

721-722 Visible light, 570, 570/

membrane, 585,

Visible spectrum, 570, 570/

Vision,

586/

570-581

Vestibular nerve, 505;, 583/,

aging and, 597

585/, 593, 595/ Vestibular nuclear complex,

cortical area for,

451,

451/',

595, 596/

437/ continues

1

1

1242 Vision,

1

Index

continued

water-soluble, 946,

cortical processing,

581

developmental aspects,

596-597 double, 564 light and,

570-571, 571/

optic nerves and, 50

optics overview,

If

570-574

VNTR

panoramic, 580

Visual association area, 437/,

440, 581 homeostatic imbalance

of,

440 Visual cortex, 437/, 440, 50 It, 579/, 580, 581 blindness and, 440

578-580, 579/ Visual pigments

Visual

fields,

Vocal cords

834/

false, 832/,

835, 835/ Vocal folds (true vocal cords),

850/ Vitamin A (retinol), 48t, 947? Vitamin Bl (thiamine), 948f

Vitamin B2 (riboflavin), 94 8f Vitamin B5 (pantothenic acid), 949? Vitamin B6 (pyridoxine), 949? Vitamin B12 (cyanocobalamin), 950?

hormone

and,

624, 624/ synthesis by epidermis, 165

Vitamin E (antisterility factor), 48t, 947? Vitamin K, 48f, 94 7? in blood clotting, 66 It, 666 Vitamins, 946-950. See also

1025-1027, 1026/ Volatile acids, 1050-1051 Volkmann's (perforating) canals, 182, 183/

93 as coenzymes, 946 deficits of, 947-950? dietary sources/RDAs/ importance in body, 947-950t excesses of, 947-950? fat-soluble, 48?, 946, 947? liver's role in storage, 978f of,

X chromosome, 1097-1098

Voltage-gated ion channels,

Na+

channels, 689, 689/ Voluntary muscle, 142, 280,

315t Voluntary nervous system. See Somatic nervous system 205/, 206/, 208/,

(ventral respiratory

78, 78/ V-tac (ventricular tachycardia),

X-linked inheritance, 1146

Water loss

X ray

1037 obligatory, 1038 sensible, 1038 water),

1037

570, 570/

297/

bases,

(ventricular tachycardia),

708 Vulva, 1085, 1085/

Wallerian degeneration, 498,

499/

665

cells).

See

1048

43

Wear-and-tear theory, 112 Weber's test, 598

fat (adipose tissue),

132

See Collagen

fibers

Whitehead, 158

Water, 8 of,

93

as universal solvent, 31,

1034 content of body, 1034 in,

36, 37/

in blood plasma, 646, 647f

intake

major sources regulation

of,

1037/ 1037-1038, of,

1038/ molecular structure, 36, 36/ output major sources of, 1037/ regulation

of,

1038-1039

White matter, 395 arrangement in CNS, 433, 433/ cerebral, 442/, 443, 444/ embryonic development, 431, 432/, 433 fiber tracts in, 442/, 443 of brain stem, 448 spinal, 472/, 473 White pulp, 778, 778/

Wisdom

teeth, 892,

892/

Withdrawal reflex, 5, 525-526, 525/ Wolff's law, 190

cavity,

10,

Yellow cast to skin (jaundice), 157 Yellow fibers. See Elastic fibers Y-linked inheritance, 1146 Yolk sac, 1073/, 1098, 1116/, 1117/,

1118

Zdisc, 284, 285/, 314? Zinc dietary sources/RDAs/

256 437/, 441

lubrication,

fibers.

marrow

deficits/excesses, 560, 954?

Wernicke's area, White blood cells (WBCs). See Leukocytes White columns, 472/, 473

White White

852t

180, 181/

Wive summation, 297-298,

acids, 43, 0149/,

of,

Y chromosome, 1097-1098 Yellow bone

of electromagnetic spectrum,

Weak Weak

(radiograph), 20£>

Yawning, mechanism

Water output, 1037 Wavelength, 587, 587/

Weeping

708

absorption

Xiphoid process, of sternum, 226, 227/, 347/

1044-1045, 1044/

(white blood Leukocytes

Vomiting (emesis), 907

Warfarin,

Xiphisternal joint, 226, 227/ regulating,

WBCs

213, 215/, 218r

VT

of,

1037/ 1036-1039, of,

Water of oxidation (metabolic

Voltage-regulated fast

VRG

mechanisms

816 Xenon CT, 20b Xerostomia, 936

Xenografts,

insensible,

397-398, 399/

Vomer bone,

1039,

1038/

hydrogen bonding

Minerals absorption

ADH,

regulation

48t parathyroid

447

1039/

Voiding (urination),

v-SNAREs,

location/functions in body,

and,

influence of

Voice production, 835-836

group), 861-862, 862/

901-902

of, 1039-1041, 1040/ hypothalamic regulation

disorders

major sources

intrinsic factor and,

Vitamin C (ascorbic acid), 948? Vitamin D (antirachitic factor), 947? calcium absorption and, 93

developmental aspects,

intake/output

398, 398/

574-578, 575/, 576/

muscles acting on, 358-361t, 359/, 361/ actions of (summary), 362-363t, 363/ Wrist drop, 513 Wrist (radiocarpal) joint, 258f movements at, 362-363?, 363/

aging and, 1058-1059

Voicebox. See Larynx

(photopigments), Vital capacity (VC), 850,

1015-1018, 1016/ Water balance

835, 835/

Vocal ligaments, 835

Voltage, 82,

1011/,

1012, 1013t,

true, 832/, 834/,

832/', 834/,

of,

1058-1059

95b

repeat),

Working memory. See Shortterm memory Wormian bones, 211 Wrist (carpus), 236-237, 236/

40-41, 41/

of,

reabsorption

number

(variable

tandem

retinal processing, 580-581, 581/ thalamic processing, 581 three-dimensional, 580 visual pathways to brain, 578-580, 579/

properties

948-950f Vitiligo, 172 Vitreous humor, 565/, 568 VLDLs (very low density lipoproteins), 977-979, 979/, 982

importance in body, 28?, 954? Zona fasciculata, 625, 625/ Zona glomerulosa, 625, 625/ Zonal inhibiting proteins (ZIPs), 1111, 1112/ Zona peilucida, 1081/', 1089, 1090/, 1112/ Zona reticularis, 625, 625/ Zonule, ciliary, 565, 565/, 569/ Zygomatic arch, 207 Zygomatic bones, 205/, 206/, 208/, 213, 214/, 218f Zygomatic nerve, 504-505? Zygomatic processes, 206/, 207, 208/, 209/, 212/', 213, 214/, 217?, 218? Zygomaticus muscles, 331/, 335?, 337/

Zygote, 1113, 1113/, 1114/ Zymogen granules, 917

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Human

pep-, peps-, pept- digest pepsin, a digestive

enzyme

of the stomach;

saw

serrat-

peptic ulcer

serratus anterior, a muscle of the chest wall that has a

jagged edge

permea- through permeate; permeable around perianal, situated around the anus phago- eat phagocyte, a cell that engulfs and digests particles or cells pheno- show, appear phenotype, the physical appearance of an in-

a hollow sinuses of the skull

per-,

sin-, sino-

peri-

soma- body somatic nervous system

somnus

splanchn- organ splanchnic nerve, autonomic supply to abdominal

dividual

phleb- vein phlebitis, inflammation of the veins pia tender pia mater, delicate inner

viscera

membrane around

the brain and

spondyl- vertebra

spinal cord

which make the

hairs

squam-

stand erect

broad platysma, broad,

flat,

flat

muscle of the neck

membrane

pleural serosa, the

pleur- side, rib

and covers the lungs plexus net, network brachial plexus, the network

that supplies the

pneumo

stria- furrow, streak striations of skeletal

of nerves

air in

the thoracic cavity

organs sucr- sweet sucrose, table sugar

sudor- sweat sudoriferous glands, the sweat glands super- above, upon superior, quality or state of being above others or

poly- multiple polymorphism, multiple forms

behind posterior, places behind (a specific) part ahead of prenatal, before birth procto- rectum, anus proctoscope, an instrument for examining the rectum pron- bent forward prone; pronate propri- one's own proprioception, awareness of body parts and

a part

after,

pre-, pro- before,

movement pseudo-

false

tumor

normal position

pub- of the pubis puberty pulmo- lung pulmonary artery, which brings blood pyrogen, a substance that induces fever

fire

quad-, quadr-

four-sided

quadratus lumborum, a muscle with a

square shape re- back, again

ren- kidney renal, renin, an net,

rectum

enzyme

salta- leap

between individuals

tissue

beam, timber

trab-

trabeculae, spicules of

bone

in

spongy bone

tissue

trans- across, through transpleural, through the pleura

trapez- table trapezius, the four-sided muscle of the upper back tri-

three trifurcation, division into three branches

trop-

turn,

change

tropic

hormones, whose targets are endocrine

glands

troph- nourish trophoblast, from which develops the

fetal

portion of

the placenta

bump on

a bone

tympan- drum tympanic membrane, the eardrum beyond ultraviolet radiation, beyond the band

vacc-

cow

of visible light

vaccine

vagin- a sheath vagina

sarco- flesh sarcomere, unit of contraction in skeletal muscle

saphenous vein, superficial vein of the

vagus wanderer the vagus nerve, which els into the abdominopelvic cavity

starts at the brain

and harden-

ing of the skin

trav-

venter, ventr-

hollow

cavity,

belly

ventral (directional term);

ventricle

ventus the wind pulmonary ventilation

seb- grease sebum, the oil of the skin

sperm semen, the discharge

of the

system semi- half semicircular, having the form of half a

male reproductive

vert- turn vertebral

column

mouth and

vestibul- a porch vestibule, the anterior entryway to the circle

nose

sens- feeling sensation; sensory

vibr- shake, quiver vibrissae, hairs of the nasal vestibule

septi- rotten

villus shaggy hair

sepsis, infection; antiseptic

septum fence nasal septum sero- serum serological tests, which

and

valen- strength valence shells of atoms

thigh and leg sclero- hard sclerodermatitis, inflammatory thickening

seed,

woven

ultra-

sanguin- blood consanguineous, indicative of a genetic relationship

semen

thyro- a shield thyroid gland

tunic- covering tunica albuginea, the covering of the testis

term)

saltatory conduction, the rapid conduction of impulses

great

of nerve impulses

rigid, tense tetanus of muscles therm- heat thermometer, an instrument used to measure heat thromb- clot thrombocyte; thrombus

tuber- swelling tuberosity, a

sagittal (directional

visible, clear

sense

tetan-

network

along myelinated neurons

saphen-

tactile

end telophase, the end of mitosis tempi-, tempo- time temporal summation tens- stretched muscle tension telo- the

tox- poison antitoxic, effective against poison

secreted by the kidney

urinary bladder

arrow

systole, contraction of the heart

tono- tension tonicity; hypertonic

endoplasmic reticulum, a network of membranous sacs within a cell retrobackward, behind retrogression, to move backward in development rheumwatery flow, change, or flux rheumatoid arthritis, rheumatic fever rhin-, rhino- nose rhinitis, inflammation of the nose ruga- fold, wrinkle rugae, the folds of the stomach, gallbladder, and sagitt-

systol- contraction

tissu-

reinfect

rect- straight rectus abdominis,

retin, retic-

tween two neurons synerg- work together synergism

tertius third peroneus tertius, one of three peroneus muscles to the lungs

pyo- pus pyocyst, a cyst that contains pus pyro-

sym-, syn- together, with synapse, the region of communication be-

tact- touch

psycho- mind, psyche psychogram, a chart of personality traits ptos- fall renal ptosis, a condition in which the kidneys drift below their

supra- above, upon supracondylar, above a condyle

tachy- rapid tachycardia, abnormally rapid heartbeat

pseudotumor, a

false

and cardiac muscle tissue tissue framework of some

sub- beneath, under sublingual, beneath the tongue

pod- foot podiatry, the treatment of foot disorders post-

of the

steno- narrow stenocoriasis, narrowing of the pupil

stroma spread out strome, the connective

arm

wind pneumothorax,

air,

squamous epithelium, squamous suture

scale, flat

strat- layer strata of the epidermis, stratified epithelium

that lines the thoracic

cavity plex-,

af-

skull

pin-, pino- drink pinocytosis, the process of a cell in small particles

platy-

ankylosing spondylitis, rheumatoid arthritis

fecting the spine

arrector pili muscles of the skin,

hair

pili

sleep insomnia, inability to sleep

sphin- squeeze sphincter

light

assess blood conditions

microvilli,

which have the appearance

of hair in

microscopy

viscero- organ, viscera visceroinhibitory, inhibiting the of the viscera

movements

viscos- sticky viscosity, resistance to flow

-logy the study of pathology, the study of changes in structure and

function brought on by disease

vitamin

vita- life

humor, the clear

vitre- glass vitreous

jelly of

the eye

-lysis

loosening or breaking

compound

viv- live in vivo

tion of a

vulv- a covering vulva, the female external genitalia

up water

zyg- a yoke, twin zygote

down

into other

hydrolysis, chemical decomposi-

compounds

as a result of taking

soft osteomalacia, a process leading to bone softening -mania obsession, compulsion erotomania, exaggeration of the sex-

-malacia

ual passions

Suffixes

-nata birth prenatal development -able able

to,

-nom govern autonomic nervous system

capable of viable, ability to live or exist

-ac referring to cardiac, referring to the heart

pain in a certain part

-algia

neuralgia, pain along the course of a

nerve -apsi juncture synapse,

where two neurons connect

-odyn pain coccygodynia, pain in the region of the coccyx -oid like, resembling cuboid, shaped as a cube -oma tumor lymphoma, a tumor of the lymphatic tissues -opia defect of the eye myopia, nearsightedness

-ary associated with, relating to coronary, associated with the heart

-ory referring

-asthen weakness myasthenia gravis, a disease involving paralysis

-pathy disease osteopathy, any disease of the bone

-atomos

indivisible

anatomy, which involves dissection

-phil, -philo like, love hydrophilic, water-attracting

-cide destroy or kill germicide,

head

an agent that

kills

germs

-crine separate endocrine organs,

which

bone matrix hormones into the

secrete

blood

-ectomy cutting out, surgical removal appendectomy, cutting out of the appendix small organelle cells

-esthesi sensation anesthesia, lack of sensation

away from

CNS

-fuge driving out

vermifuge, a substance that expels

worms

of the

intestine

an agent that

initiates

pathogen, any agent that produces

disease

glue neuroglia, the connective tissue of the nervous system -gram data that are systematically recorded, a record electrocardiogram, a recording showing action of the heart -graph an instrument used for recording data or writing electrocardiograph, an instrument used to make an electrocardiogram -ia condition insomnia, condition of not being able to sleep -glea, -glia

-iatrics

medical specialty

geriatrics, the

branch of medicine dealing with

disease associated with old age

-ism condition hyperthyroidism -itis

gastritis, inflammation of the stomach husk sarcolemma, the plasma membrane of a mus-

inflammation

-lemma

sheath,

cle cell

grow neoplasia, an abnormal growth -plasm form, shape cytoplasm -plasty reconstruction of a part, plastic surgery rhinoplasty, recon-

struction of the nose through surgery

body or

limbs

abnormal or excessive discharge metrorrhagia, uterine hemorrhage -rrhea flow or discharge diarrhea, abnormal emptying of the bowels -scope instrument used for examination stethoscope, instrument used to listen to sounds of parts of the body -some body chromosome -sorb suck in absorb -stalsis compression peristalsis, muscular contractions that propel -rrhagia

carry efferent nerves, nerves carrying impulses

-form, -forma shape cribriform plate of the ethmoid bone

-gen

cavities

-plegia paralysis paraplegia, paralysis of the lower half of the

-emia condition of the blood anemia, deficiency of red blood

the

dominal

-phylax guard, preserve anaphylaxis, prophylactic -plas

-dips thirst, dry polydipsia, excessive thirst associated with diabetes

-ferent

molecules

-phobia fear acrophobia, fear of heights •phragm partition diaphragm, which separates the thoracic and ab-

occipital

-clast break osteoclast, a cell that dissolves

-ell, -elle

of auditory, referring to hearing

-phasia speech aphasia, lack of ability to speak

-bryo swollen embryo -cipit

to,

food along the digestive tract -stasis arrest, fixation

come

hemostasis, arrest of bleeding

between the cells -stomy estabhshment of an artificial opening enterostomy, the formation of an artificial opening into the intestine through the abdominal wall -tegm cover integument -tomy to cut appendectomy, surgical removal of the appendix -trud thrust protrude, detrusor muscle -ty condition of, state immunity, condition of being resistant to in-stitia

to stand interstitial fluid,

fection or disease -uria urine polyuria, passage of

-zyme ferment enzyme

an excessive amount of urine

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