This week's reading is section 44.1 – 44.5 (all sections of chapter 44) of the course textbook, which is accessible through the Syllabus or through the course's "Textbooks" page. Grading: Answers shou
Biology
SENIOR CONTRIBUTING A UTHORS
C ONNIE R YE , EAST M ISSISSIPPI C OMMUNITY C OLLEGE
R OBERT W ISE , U NIVERSITY OF W ISCONSIN , O SHKOSH
V LADIMIR JURUKOVSKI , SUFFOLK C OUNTY C OMMUNITY C OLLEGE
JEAN D ESAIX , U NIVERSITY OF N ORTH C AROLINA AT C HAPEL H ILL
JUNG C HOI , G EORGIA INSTITUTE OF TECHNOLOGY
YAEL A VISSAR , R HODE ISLAND C OLLEGE
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39 | THE RESPIRATORY
SYSTEM
Figure 39.1 Lungs, which appear as nearly transparent tissue surrounding the heart in this X-ray of a dog (left), are
the central organs of the respiratory system. The left lung is smaller than the right lung to accommodate space for the
heart. A dog’s nose (right) has a slit on the side of each nostril. When tracking a scent, the slits open, blocking the
front of the nostrils. This allows the dog to exhale though the now-open area on the side of the nostrils without losing
the scent that is being followed. (credit a: modification of work by Geoff Stearns; credit b: modification of work by Cory
Zanker)
Chapter Outline
39.1: Systems of Gas Exchange
39.2: Gas Exchange across Respiratory Surfaces
39.3: Breathing
39.4: Transport of Gases in Human Bodily Fluids
Introduction
Breathing is an involuntary event. How often a breath is taken and how much air is inhaled or exhaled are tightly regulated
by the respiratory center in the brain. Humans, when they aren’t exerting themselves, breathe approximately 15 times per
minute on average. Canines, like the dog in Figure 39.1 , have a respiratory rate of about 15–30 breaths per minute. With
every inhalation, air fills the lungs, and with every exhalation, air rushes back out. That air is doing more than just inflating
and deflating the lungs in the chest cavity. The air contains oxygen that crosses the lung tissue, enters the bloodstream,
and travels to organs and tissues. Oxygen (O 2) enters the cells where it is used for metabolic reactions that produce ATP, a
high-energy compound. At the same time, these reactions release carbon dioxide (CO 2) as a by-product. CO 2is toxic and
must be eliminated. Carbon dioxide exits the cells, enters the bloodstream, travels back to the lungs, and is expired out of
the body during exhalation.
Chapter 39 | The Respiratory System 1135 39.1 | Systems of Gas Exchange
By the end of this section, you will be able to:
• Describe the passage of air from the outside environment to the lungs
• Explain how the lungs are protected from particulate matter
The primary function of the respiratory system is to deliver oxygen to the cells of the body’s tissues and remove carbon
dioxide, a cell waste product. The main structures of the human respiratory system are the nasal cavity, the trachea, and
lungs.
All aerobic organisms require oxygen to carry out their metabolic functions. Along the evolutionary tree, different
organisms have devised different means of obtaining oxygen from the surrounding atmosphere. The environment in which
the animal lives greatly determines how an animal respires. The complexity of the respiratory system is correlated with the
size of the organism. As animal size increases, diffusion distances increase and the ratio of surface area to volume drops.
In unicellular organisms, diffusion across the cell membrane is sufficient for supplying oxygen to the cell ( Figure 39.2 ).
Diffusion is a slow, passive transport process. In order for diffusion to be a feasible means of providing oxygen to the cell,
the rate of oxygen uptake must match the rate of diffusion across the membrane. In other words, if the cell were very large
or thick, diffusion would not be able to provide oxygen quickly enough to the inside of the cell. Therefore, dependence
on diffusion as a means of obtaining oxygen and removing carbon dioxide remains feasible only for small organisms or
those with highly-flattened bodies, such as many flatworms (Platyhelminthes). Larger organisms had to evolve specialized
respiratory tissues, such as gills, lungs, and respiratory passages accompanied by complex circulatory systems, to transport
oxygen throughout their entire body.
Figure 39.2 The cell of the unicellular algae Ventricaria ventricosa is one of the largest known, reaching one to five
centimeters in diameter. Like all single-celled organisms, V. ventricosa exchanges gases across the cell membrane.
Direct Diffusion
For small multicellular organisms, diffusion across the outer membrane is sufficient to meet their oxygen needs. Gas
exchange by direct diffusion across surface membranes is efficient for organisms less than 1 mm in diameter. In simple
organisms, such as cnidarians and flatworms, every cell in the body is close to the external environment. Their cells
are kept moist and gases diffuse quickly via direct diffusion. Flatworms are small, literally flat worms, which ‘breathe’
through diffusion across the outer membrane ( Figure 39.3 ). The flat shape of these organisms increases the surface area for
diffusion, ensuring that each cell within the body is close to the outer membrane surface and has access to oxygen. If the
flatworm had a cylindrical body, then the cells in the center would not be able to get oxygen.
1136 Chapter 39 | The Respiratory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 39.3 This flatworm’s process of respiration works by diffusion across the outer membrane. (credit: Stephen
Childs)
Skin and Gills
Earthworms and amphibians use their skin (integument) as a respiratory organ. A dense network of capillaries lies just
below the skin and facilitates gas exchange between the external environment and the circulatory system. The respiratory
surface must be kept moist in order for the gases to dissolve and diffuse across cell membranes.
Organisms that live in water need to obtain oxygen from the water. Oxygen dissolves in water but at a lower concentration
than in the atmosphere. The atmosphere has roughly 21 percent oxygen. In water, the oxygen concentration is much smaller
than that. Fish and many other aquatic organisms have evolved gills to take up the dissolved oxygen from water ( Figure
39.4 ). Gills are thin tissue filaments that are highly branched and folded. When water passes over the gills, the dissolved
oxygen in water rapidly diffuses across the gills into the bloodstream. The circulatory system can then carry the oxygenated
blood to the other parts of the body. In animals that contain coelomic fluid instead of blood, oxygen diffuses across the gill
surfaces into the coelomic fluid. Gills are found in mollusks, annelids, and crustaceans.
Figure 39.4 This common carp, like many other aquatic organisms, has gills that allow it to obtain oxygen from water.
(credit: "Guitardude012"/Wikimedia Commons)
The folded surfaces of the gills provide a large surface area to ensure that the fish gets sufficient oxygen. Diffusion is a
process in which material travels from regions of high concentration to low concentration until equilibrium is reached. In
this case, blood with a low concentration of oxygen molecules circulates through the gills. The concentration of oxygen
molecules in water is higher than the concentration of oxygen molecules in gills. As a result, oxygen molecules diffuse from
water (high concentration) to blood (low concentration), as shown in Figure 39.5 . Similarly, carbon dioxide molecules in
the blood diffuse from the blood (high concentration) to water (low concentration).
Chapter 39 | The Respiratory System 1137 Figure 39.5 As water flows over the gills, oxygen is transferred to blood via the veins. (credit "fish": modification of
work by Duane Raver, NOAA)
Tracheal Systems
Insect respiration is independent of its circulatory system; therefore, the blood does not play a direct role in oxygen
transport. Insects have a highly specialized type of respiratory system called the tracheal system, which consists of a
network of small tubes that carries oxygen to the entire body. The tracheal system is the most direct and efficient respiratory
system in active animals. The tubes in the tracheal system are made of a polymeric material called chitin.
Insect bodies have openings, called spiracles, along the thorax and abdomen. These openings connect to the tubular network,
allowing oxygen to pass into the body ( Figure 39.6 ) and regulating the diffusion of CO 2and water vapor. Air enters and
leaves the tracheal system through the spiracles. Some insects can ventilate the tracheal system with body movements.
Figure 39.6 Insects perform respiration via a tracheal system.
Mammalian Systems
In mammals, pulmonary ventilation occurs via inhalation (breathing). During inhalation, air enters the body through the
nasal cavity located just inside the nose ( Figure 39.7 ). As air passes through the nasal cavity, the air is warmed to body
temperature and humidified. The respiratory tract is coated with mucus to seal the tissues from direct contact with air. Mucus
is high in water. As air crosses these surfaces of the mucous membranes, it picks up water. These processes help equilibrate
the air to the body conditions, reducing any damage that cold, dry air can cause. Particulate matter that is floating in the air
is removed in the nasal passages via mucus and cilia. The processes of warming, humidifying, and removing particles are
important protective mechanisms that prevent damage to the trachea and lungs. Thus, inhalation serves several purposes in
addition to bringing oxygen into the respiratory system.
1138 Chapter 39 | The Respiratory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 39.7 Air enters the respiratory system through the nasal cavity and pharynx, and then passes through the
trachea and into the bronchi, which bring air into the lungs. (credit: modification of work by NCI)
Which of the following statements about the mammalian respiratory system is false?
a. When we breathe in, air travels from the pharynx to the trachea.
b. The bronchioles branch into bronchi.
c. Alveolar ducts connect to alveolar sacs.
d. Gas exchange between the lung and blood takes place in the alveolus.
From the nasal cavity, air passes through the pharynx (throat) and the larynx (voice box), as it makes its way to the trachea
(Figure 39.7 ). The main function of the trachea is to funnel the inhaled air to the lungs and the exhaled air back out of
the body. The human trachea is a cylinder about 10 to 12 cm long and 2 cm in diameter that sits in front of the esophagus
and extends from the larynx into the chest cavity where it divides into the two primary bronchi at the midthorax. It is
made of incomplete rings of hyaline cartilage and smooth muscle ( Figure 39.8 ). The trachea is lined with mucus-producing
goblet cells and ciliated epithelia. The cilia propel foreign particles trapped in the mucus toward the pharynx. The cartilage
provides strength and support to the trachea to keep the passage open. The smooth muscle can contract, decreasing the
trachea’s diameter, which causes expired air to rush upwards from the lungs at a great force. The forced exhalation helps
expel mucus when we cough. Smooth muscle can contract or relax, depending on stimuli from the external environment or
the body’s nervous system.
Chapter 39 | The Respiratory System 1139 Figure 39.8 The trachea and bronchi are made of incomplete rings of cartilage. (credit: modification of work by Gray's
Anatomy)
Lungs: Bronchi and Alveoli
The end of the trachea bifurcates (divides) to the right and left lungs. The lungs are not identical. The right lung is larger
and contains three lobes, whereas the smaller left lung contains two lobes ( Figure 39.9 ). The muscular diaphragm , which
facilitates breathing, is inferior to (below) the lungs and marks the end of the thoracic cavity.
Figure 39.9 The trachea bifurcates into the right and left bronchi in the lungs. The right lung is made of three lobes
and is larger. To accommodate the heart, the left lung is smaller and has only two lobes.
In the lungs, air is diverted into smaller and smaller passages, or bronchi . Air enters the lungs through the two primary
(main) bronchi (singular: bronchus). Each bronchus divides into secondary bronchi, then into tertiary bronchi, which
in turn divide, creating smaller and smaller diameter bronchioles as they split and spread through the lung. Like the
trachea, the bronchi are made of cartilage and smooth muscle. At the bronchioles, the cartilage is replaced with elastic
fibers. Bronchi are innervated by nerves of both the parasympathetic and sympathetic nervous systems that control
muscle contraction (parasympathetic) or relaxation (sympathetic) in the bronchi and bronchioles, depending on the nervous
system’s cues. In humans, bronchioles with a diameter smaller than 0.5 mm are the respiratory bronchioles . They lack
cartilage and therefore rely on inhaled air to support their shape. As the passageways decrease in diameter, the relative
amount of smooth muscle increases.
The terminal bronchioles subdivide into microscopic branches called respiratory bronchioles. The respiratory bronchioles
subdivide into several alveolar ducts. Numerous alveoli and alveolar sacs surround the alveolar ducts. The alveolar sacs
resemble bunches of grapes tethered to the end of the bronchioles ( Figure 39.10 ). In the acinar region, the alveolar ducts
1140 Chapter 39 | The Respiratory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 are attached to the end of each bronchiole. At the end of each duct are approximately 100 alveolar sacs , each containing 20
to 30 alveoli that are 200 to 300 microns in diameter. Gas exchange occurs only in alveoli. Alveoli are made of thin-walled
parenchymal cells, typically one-cell thick, that look like tiny bubbles within the sacs. Alveoli are in direct contact with
capillaries (one-cell thick) of the circulatory system. Such intimate contact ensures that oxygen will diffuse from alveoli
into the blood and be distributed to the cells of the body. In addition, the carbon dioxide that was produced by cells as a
waste product will diffuse from the blood into alveoli to be exhaled. The anatomical arrangement of capillaries and alveoli
emphasizes the structural and functional relationship of the respiratory and circulatory systems. Because there are so many
alveoli (~300 million per lung) within each alveolar sac and so many sacs at the end of each alveolar duct, the lungs have a
sponge-like consistency. This organization produces a very large surface area that is available for gas exchange. The surface
area of alveoli in the lungs is approximately 75 m 2. This large surface area, combined with the thin-walled nature of the
alveolar parenchymal cells, allows gases to easily diffuse across the cells.
Figure 39.10 Terminal bronchioles are connected by respiratory bronchioles to alveolar ducts and alveolar sacs. Each
alveolar sac contains 20 to 30 spherical alveoli and has the appearance of a bunch of grapes. Air flows into the atrium
of the alveolar sac, then circulates into alveoli where gas exchange occurs with the capillaries. Mucous glands secrete
mucous into the airways, keeping them moist and flexible. (credit: modification of work by Mariana Ruiz Villareal)
Watch the following video (http://openstaxcollege.org/l/lungs_pulmonary) to review the respiratory system.
Protective Mechanisms
The air that organisms breathe contains particulate matter such as dust, dirt, viral particles, and bacteria that can damage
the lungs or trigger allergic immune responses. The respiratory system contains several protective mechanisms to avoid
problems or tissue damage. In the nasal cavity, hairs and mucus trap small particles, viruses, bacteria, dust, and dirt to
prevent their entry.
Chapter 39 | The Respiratory System 1141 If particulates do make it beyond the nose, or enter through the mouth, the bronchi and bronchioles of the lungs also contain
several protective devices. The lungs produce mucus —a sticky substance made of mucin , a complex glycoprotein, as well
as salts and water—that traps particulates. The bronchi and bronchioles contain cilia, small hair-like projections that line
the walls of the bronchi and bronchioles ( Figure 39.11 ). These cilia beat in unison and move mucus and particles out of the
bronchi and bronchioles back up to the throat where it is swallowed and eliminated via the esophagus.
In humans, for example, tar and other substances in cigarette smoke destroy or paralyze the cilia, making the removal of
particles more difficult. In addition, smoking causes the lungs to produce more mucus, which the damaged cilia are not able
to move. This causes a persistent cough, as the lungs try to rid themselves of particulate matter, and makes smokers more
susceptible to respiratory ailments.
Figure 39.11 The bronchi and bronchioles contain cilia that help move mucus and other particles out of the lungs.
(credit: Louisa Howard, modification of work by Dartmouth Electron Microscope Facility)
39.2 | Gas Exchange across Respiratory Surfaces
By the end of this section, you will be able to:
• Name and describe lung volumes and capacities
• Understand how gas pressure influences how gases move into and out of the body
The structure of the lung maximizes its surface area to increase gas diffusion. Because of the enormous number of alveoli
(approximately 300 million in each human lung), the surface area of the lung is very large (75 m 2). Having such a large
surface area increases the amount of gas that can diffuse into and out of the lungs.
Basic Principles of Gas Exchange
Gas exchange during respiration occurs primarily through diffusion. Diffusion is a process in which transport is driven by
a concentration gradient. Gas molecules move from a region of high concentration to a region of low concentration. Blood
that is low in oxygen concentration and high in carbon dioxide concentration undergoes gas exchange with air in the lungs.
The air in the lungs has a higher concentration of oxygen than that of oxygen-depleted blood and a lower concentration of
carbon dioxide. This concentration gradient allows for gas exchange during respiration.
Partial pressure is a measure of the concentration of the individual components in a mixture of gases. The total pressure
exerted by the mixture is the sum of the partial pressures of the components in the mixture. The rate of diffusion of a gas is
proportional to its partial pressure within the total gas mixture. This concept is discussed further in detail below.
Lung Volumes and Capacities
Different animals have different lung capacities based on their activities. Cheetahs have evolved a much higher lung
capacity than humans; it helps provide oxygen to all the muscles in the body and allows them to run very fast. Elephants
1142 Chapter 39 | The Respiratory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 also have a high lung capacity. In this case, it is not because they run fast but because they have a large body and must be
able to take up oxygen in accordance with their body size.
Human lung size is determined by genetics, gender, and height. At maximal capacity, an average lung can hold almost six
liters of air, but lungs do not usually operate at maximal capacity. Air in the lungs is measured in terms of lung volumes
and lung capacities (Figure 39.12 and Table 39.1 ). Volume measures the amount of air for one function (such as inhalation
or exhalation). Capacity is any two or more volumes (for example, how much can be inhaled from the end of a maximal
exhalation).
Figure 39.12 Human lung volumes and capacities are shown. The total lung capacity of the adult male is six liters.
Tidal volume is the volume of air inhaled in a single, normal breath. Inspiratory capacity is the amount of air taken in
during a deep breath, and residual volume is the amount of air left in the lungs after forceful respiration.
Lung Volumes and Capacities (Avg Adult Male)
Volume/
Capacity Definition Volume
(liters) Equations
Tidal volume (TV) Amount of air inhaled during a normal breath 0.5 -
Expiratory reserve
volume (ERV)
Amount of air that can be exhaled after a normal
exhalation 1.2 -
Inspiratory reserve
volume (IRV)
Amount of air that can be further inhaled after a normal
inhalation 3.1 -
Residual volume
(RV) Air left in the lungs after a forced exhalation 1.2 -
Vital capacity (VC) Maximum amount of air that can be moved in or out of
the lungs in a single respiratory cycle 4.8 ERV+TV+IRV
Inspiratory capacity
(IC)
Volume of air that can be inhaled in addition to a
normal exhalation 3.6 TV+IRV
Functional residual
capacity (FRC) Volume of air remaining after a normal exhalation 2.4 ERV+RV
Total lung capacity
(TLC)
Total volume of air in the lungs after a maximal
inspiration 6.0 RV+ERV+TV+IRV
Forced expiratory
volume (FEV1)
How much air can be forced out of the lungs over a
specific time period, usually one second ~4.1 to 5.5 -
Table 39.1
Chapter 39 | The Respiratory System 1143 The volume in the lung can be divided into four units: tidal volume, expiratory reserve volume, inspiratory reserve volume,
and residual volume. Tidal volume (TV) measures the amount of air that is inspired and expired during a normal breath.
On average, this volume is around one-half liter, which is a little less than the capacity of a 20-ounce drink bottle. The
expiratory reserve volume (ERV) is the additional amount of air that can be exhaled after a normal exhalation. It is the
reserve amount that can be exhaled beyond what is normal. Conversely, the inspiratory reserve volume (IRV) is the
additional amount of air that can be inhaled after a normal inhalation. The residual volume (RV) is the amount of air that is
left after expiratory reserve volume is exhaled. The lungs are never completely empty: There is always some air left in the
lungs after a maximal exhalation. If this residual volume did not exist and the lungs emptied completely, the lung tissues
would stick together and the energy necessary to re-inflate the lung could be too great to overcome. Therefore, there is
always some air remaining in the lungs. Residual volume is also important for preventing large fluctuations in respiratory
gases (O 2and CO 2). The residual volume is the only lung volume that cannot be measured directly because it is impossible
to completely empty the lung of air. This volume can only be calculated rather than measured.
Capacities are measurements of two or more volumes. The vital capacity (VC) measures the maximum amount of air that
can be inhaled or exhaled during a respiratory cycle. It is the sum of the expiratory reserve volume, tidal volume, and
inspiratory reserve volume. The inspiratory capacity (IC) is the amount of air that can be inhaled after the end of a normal
expiration. It is, therefore, the sum of the tidal volume and inspiratory reserve volume. The functional residual capacity
(FRC) includes the expiratory reserve volume and the residual volume. The FRC measures the amount of additional air that
can be exhaled after a normal exhalation. Lastly, the total lung capacity (TLC) is a measurement of the total amount of air
that the lung can hold. It is the sum of the residual volume, expiratory reserve volume, tidal volume, and inspiratory reserve
volume.
Lung volumes are measured by a technique called spirometry . An important measurement taken during spirometry is the
forced expiratory volume (FEV) , which measures how much air can be forced out of the lung over a specific period,
usually one second (FEV1). In addition, the forced vital capacity (FVC), which is the total amount of air that can be forcibly
exhaled, is measured. The ratio of these values ( FEV1/FVC ratio ) is used to diagnose lung diseases including asthma,
emphysema, and fibrosis. If the FEV1/FVC ratio is high, the lungs are not compliant (meaning they are stiff and unable
to bend properly), and the patient most likely has lung fibrosis. Patients exhale most of the lung volume very quickly.
Conversely, when the FEV1/FVC ratio is low, there is resistance in the lung that is characteristic of asthma. In this instance,
it is hard for the patient to get the air out of his or her lungs, and it takes a long time to reach the maximal exhalation volume.
In either case, breathing is difficult and complications arise.
Respiratory Therapist
Respiratory therapists or respiratory practitioners evaluate and treat patients with lung and cardiovascular
diseases. They work as part of a medical team to develop treatment plans for patients. Respiratory
therapists may treat premature babies with underdeveloped lungs, patients with chronic conditions such
as asthma, or older patients suffering from lung disease such as emphysema and chronic obstructive
pulmonary disease (COPD). They may operate advanced equipment such as compressed gas delivery
systems, ventilators, blood gas analyzers, and resuscitators. Specialized programs to become a respiratory
therapist generally lead to a bachelor’s degree with a respiratory therapist specialty. Because of a growing
aging population, career opportunities as a respiratory therapist are expected to remain strong.
Gas Pressure and Respiration
The respiratory process can be better understood by examining the properties of gases. Gases move freely, but gas particles
are constantly hitting the walls of their vessel, thereby producing gas pressure.
Air is a mixture of gases, primarily nitrogen (N 2; 78.6 percent), oxygen (O 2; 20.9 percent), water vapor (H 2O; 0.5 percent),
and carbon dioxide (CO 2; 0.04 percent). Each gas component of that mixture exerts a pressure. The pressure for an
individual gas in the mixture is the partial pressure of that gas. Approximately 21 percent of atmospheric gas is oxygen.
Carbon dioxide, however, is found in relatively small amounts, 0.04 percent. The partial pressure for oxygen is much greater
than that of carbon dioxide. The partial pressure of any gas can be calculated by:
P = (P atm ) × (percent content in mixture).
Patm , the atmospheric pressure, is the sum of all of the partial pressures of the atmospheric gases added together,
1144 Chapter 39 | The Respiratory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Patm = P N2 + P O2 + P H2O + P CO 2= 760 mm Hg
× (percent content in mixture).
The pressure of the atmosphere at sea level is 760 mm Hg. Therefore, the partial pressure of oxygen is:
PO2= (760 mm Hg) (0.21) = 160 mm Hg
and for carbon dioxide:
PCO 2= (760 mm Hg) (0.0004) = 0.3 mm Hg.
At high altitudes, P atm decreases but concentration does not change; the partial pressure decrease is due to the reduction in
Patm .
When the air mixture reaches the lung, it has been humidified. The pressure of the water vapor in the lung does not change
the pressure of the air, but it must be included in the partial pressure equation. For this calculation, the water pressure (47
mm Hg) is subtracted from the atmospheric pressure:
760 mm Hg − 47 mm Hg = 713 mm Hg
and the partial pressure of oxygen is:
(760 mm Hg − 47 mm Hg) × 0.21 = 150 mm Hg.
These pressures determine the gas exchange, or the flow of gas, in the system. Oxygen and carbon dioxide will flow
according to their pressure gradient from high to low. Therefore, understanding the partial pressure of each gas will aid in
understanding how gases move in the respiratory system.
Gas Exchange across the Alveoli
In the body, oxygen is used by cells of the body’s tissues and carbon dioxide is produced as a waste product. The ratio of
carbon dioxide production to oxygen consumption is the respiratory quotient (RQ) . RQ varies between 0.7 and 1.0. If just
glucose were used to fuel the body, the RQ would equal one. One mole of carbon dioxide would be produced for every mole
of oxygen consumed. Glucose, however, is not the only fuel for the body. Protein and fat are also used as fuels for the body.
Because of this, less carbon dioxide is produced than oxygen is consumed and the RQ is, on average, about 0.7 for fat and
about 0.8 for protein.
The RQ is used to calculate the partial pressure of oxygen in the alveolar spaces within the lung, the alveolar PO2Above,
the partial pressure of oxygen in the lungs was calculated to be 150 mm Hg. However, lungs never fully deflate with an
exhalation; therefore, the inspired air mixes with this residual air and lowers the partial pressure of oxygen within the
alveoli. This means that there is a lower concentration of oxygen in the lungs than is found in the air outside the body.
Knowing the RQ, the partial pressure of oxygen in the alveoli can be calculated:
alveolar P O2= inspired P O2− ( alveolar P O2 RQ )
With an RQ of 0.8 and a PCO 2in the alveoli of 40 mm Hg, the alveolar PO2is equal to:
alveolar P O2 = 150 mm Hg − ( 40 mm Hg
0.8 ) = mm Hg.
Notice that this pressure is less than the external air. Therefore, the oxygen will flow from the inspired air in the lung ( PO2
= 150 mm Hg) into the bloodstream ( PO2= 100 mm Hg) ( Figure 39.13 ).
In the lungs, oxygen diffuses out of the alveoli and into the capillaries surrounding the alveoli. Oxygen (about 98 percent)
binds reversibly to the respiratory pigment hemoglobin found in red blood cells (RBCs). RBCs carry oxygen to the tissues
where oxygen dissociates from the hemoglobin and diffuses into the cells of the tissues. More specifically, alveolar PO2
is higher in the alveoli ( PALVO 2= 100 mm Hg) than blood PO2(40 mm Hg) in the capillaries. Because this pressure
gradient exists, oxygen diffuses down its pressure gradient, moving out of the alveoli and entering the blood of the
Chapter 39 | The Respiratory System 1145 capillaries where O 2binds to hemoglobin. At the same time, alveolar PCO 2is lower PALVO 2= 40 mm Hg than blood
PCO 2= (45 mm Hg). CO 2diffuses down its pressure gradient, moving out of the capillaries and entering the alveoli.
Oxygen and carbon dioxide move independently of each other; they diffuse down their own pressure gradients. As blood
leaves the lungs through the pulmonary veins, the venous PO2= 100 mm Hg, whereas the venous PCO 2= 40 mm Hg. As
blood enters the systemic capillaries, the blood will lose oxygen and gain carbon dioxide because of the pressure difference
of the tissues and blood. In systemic capillaries, PO2= 100 mm Hg, but in the tissue cells, PO2= 40 mm Hg. This pressure
gradient drives the diffusion of oxygen out of the capillaries and into the tissue cells. At the same time, blood PCO 2= 40
mm Hg and systemic tissue PCO 2= 45 mm Hg. The pressure gradient drives CO 2out of tissue cells and into the capillaries.
The blood returning to the lungs through the pulmonary arteries has a venous PO2= 40 mm Hg and a PCO 2= 45 mm Hg.
The blood enters the lung capillaries where the process of exchanging gases between the capillaries and alveoli begins again
(Figure 39.13 ).
Figure 39.13 The partial pressures of oxygen and carbon dioxide change as blood moves through the body.
Which of the following statements is false?
a. In the tissues, PO2drops as blood passes from the arteries to the veins, while PCO 2increases.
b. Blood travels from the lungs to the heart to body tissues, then back to the heart, then the lungs.
c. Blood travels from the lungs to the heart to body tissues, then back to the lungs, then the heart.
d. PO2is higher in air than in the lungs.
In short, the change in partial pressure from the alveoli to the capillaries drives the oxygen into the tissues and the carbon
dioxide into the blood from the tissues. The blood is then transported to the lungs where differences in pressure in the alveoli
result in the movement of carbon dioxide out of the blood into the lungs, and oxygen into the blood.
1146 Chapter 39 | The Respiratory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Watch this video (http://openstaxcollege.org/l/spirometry) to learn how to carry out spirometry.
39.3 | Breathing
By the end of this section, you will be able to:
• Describe how the structures of the lungs and thoracic cavity control the mechanics of breathing
• Explain the importance of compliance and resistance in the lungs
• Discuss problems that may arise due to a V/Q mismatch
Mammalian lungs are located in the thoracic cavity where they are surrounded and protected by the rib cage, intercostal
muscles, and bound by the chest wall. The bottom of the lungs is contained by the diaphragm, a skeletal muscle that
facilitates breathing. Breathing requires the coordination of the lungs, the chest wall, and most importantly, the diaphragm.
Types of Breathing
Amphibians have evolved multiple ways of breathing. Young amphibians, like tadpoles, use gills to breathe, and they don’t
leave the water. Some amphibians retain gills for life. As the tadpole grows, the gills disappear and lungs grow. These
lungs are primitive and not as evolved as mammalian lungs. Adult amphibians are lacking or have a reduced diaphragm, so
breathing via lungs is forced. The other means of breathing for amphibians is diffusion across the skin. To aid this diffusion,
amphibian skin must remain moist.
Birds face a unique challenge with respect to breathing: They fly. Flying consumes a great amount of energy; therefore, birds
require a lot of oxygen to aid their metabolic processes. Birds have evolved a respiratory system that supplies them with
the oxygen needed to enable flying. Similar to mammals, birds have lungs, which are organs specialized for gas exchange.
Oxygenated air, taken in during inhalation, diffuses across the surface of the lungs into the bloodstream, and carbon dioxide
diffuses from the blood into the lungs and expelled during exhalation. The details of breathing between birds and mammals
differ substantially.
In addition to lungs, birds have air sacs inside their body. Air flows in one direction from the posterior air sacs to the lungs
and out of the anterior air sacs. The flow of air is in the opposite direction from blood flow, and gas exchange takes place
much more efficiently. This type of breathing enables birds to obtain the requisite oxygen, even at higher altitudes where
the oxygen concentration is low. This directionality of airflow requires two cycles of air intake and exhalation to completely
get the air out of the lungs.
Chapter 39 | The Respiratory System 1147 Avian Respiration
Birds have evolved a respiratory system that enables them to fly. Flying is a high-energy process and
requires a lot of oxygen. Furthermore, many birds fly in high altitudes where the concentration of oxygen in
low. How did birds evolve a respiratory system that is so unique?
Decades of research by paleontologists have shown that birds evolved from therapods, meat-eating
dinosaurs ( Figure 39.14 ). In fact, fossil evidence shows that meat-eating dinosaurs that lived more than 100
million years ago had a similar flow-through respiratory system with lungs and air sacs. Archaeopteryx and
Xiaotingia , for example, were flying dinosaurs and are believed to be early precursors of birds.
Figure 39.14 (a) Birds have a flow-through respiratory system in which air flows unidirectionally from the posterior
sacs into the lungs, then into the anterior air sacs. The air sacs connect to openings in hollow bones. (b)
Dinosaurs, from which birds descended, have similar hollow bones and are believed to have had a similar
respiratory system. (credit b: modification of work by Zina Deretsky, National Science Foundation)
Most of us consider that dinosaurs are extinct. However, modern birds are descendants of avian dinosaurs.
The respiratory system of modern birds has been evolving for hundreds of millions of years.
1148 Chapter 39 | The Respiratory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 All mammals have lungs that are the main organs for breathing. Lung capacity has evolved to support the animal’s activities.
During inhalation, the lungs expand with air, and oxygen diffuses across the lung’s surface and enters the bloodstream.
During exhalation, the lungs expel air and lung volume decreases. In the next few sections, the process of human breathing
will be explained.
The Mechanics of Human Breathing
Boyle’s Law is the gas law that states that in a closed space, pressure and volume are inversely related. As volume decreases,
pressure increases and vice versa ( Figure 39.15 ). The relationship between gas pressure and volume helps to explain the
mechanics of breathing.
Figure 39.15 This graph shows data from Boyle’s original 1662 experiment, which shows that pressure and volume
are inversely related. No units are given as Boyle used arbitrary units in his experiments.
There is always a slightly negative pressure within the thoracic cavity, which aids in keeping the airways of the lungs
open. During inhalation, volume increases as a result of contraction of the diaphragm, and pressure decreases (according
to Boyle’s Law). This decrease of pressure in the thoracic cavity relative to the environment makes the cavity less than
the atmosphere ( Figure 39.16 a). Because of this drop in pressure, air rushes into the respiratory passages. To increase the
volume of the lungs, the chest wall expands. This results from the contraction of the intercostal muscles , the muscles that
are connected to the rib cage. Lung volume expands because the diaphragm contracts and the intercostals muscles contract,
thus expanding the thoracic cavity. This increase in the volume of the thoracic cavity lowers pressure compared to the
atmosphere, so air rushes into the lungs, thus increasing its volume. The resulting increase in volume is largely attributed to
an increase in alveolar space, because the bronchioles and bronchi are stiff structures that do not change in size.
Figure 39.16 The lungs, chest wall, and diaphragm are all involved in respiration, both (a) inhalation and (b) expiration.
(credit: modification of work by Mariana Ruiz Villareal)
The chest wall expands out and away from the lungs. The lungs are elastic; therefore, when air fills the lungs, the elastic
recoil within the tissues of the lung exerts pressure back toward the interior of the lungs. These outward and inward forces
Chapter 39 | The Respiratory System 1149 compete to inflate and deflate the lung with every breath. Upon exhalation, the lungs recoil to force the air out of the lungs,
and the intercostal muscles relax, returning the chest wall back to its original position ( Figure 39.16 b). The diaphragm
also relaxes and moves higher into the thoracic cavity. This increases the pressure within the thoracic cavity relative to
the environment, and air rushes out of the lungs. The movement of air out of the lungs is a passive event. No muscles are
contracting to expel the air.
Each lung is surrounded by an invaginated sac. The layer of tissue that covers the lung and dips into spaces is called the
visceral pleura . A second layer of parietal pleura lines the interior of the thorax ( Figure 39.17 ). The space between these
layers, the intrapleural space , contains a small amount of fluid that protects the tissue and reduces the friction generated
from rubbing the tissue layers together as the lungs contract and relax. Pleurisy results when these layers of tissue become
inflamed; it is painful because the inflammation increases the pressure within the thoracic cavity and reduces the volume of
the lung.
Figure 39.17 A tissue layer called pleura surrounds the lung and interior of the thoracic cavity. (credit: modification of
work by NCI)
View (http://openstaxcollege.org/l/boyle_breathing) how Boyle’s Law is related to breathing and watch this video
(http://openstaxcollege.org/l/boyles_law) on Boyle’s Law.
The Work of Breathing
The number of breaths per minute is the respiratory rate . On average, under non-exertion conditions, the human respiratory
rate is 12–15 breaths/minute. The respiratory rate contributes to the alveolar ventilation , or how much air moves into
and out of the alveoli. Alveolar ventilation prevents carbon dioxide buildup in the alveoli. There are two ways to keep
the alveolar ventilation constant: increase the respiratory rate while decreasing the tidal volume of air per breath (shallow
breathing), or decrease the respiratory rate while increasing the tidal volume per breath. In either case, the ventilation
1150 Chapter 39 | The Respiratory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 remains the same, but the work done and type of work needed are quite different. Both tidal volume and respiratory rate are
closely regulated when oxygen demand increases.
There are two types of work conducted during respiration, flow-resistive and elastic work. Flow-resistive refers to the work
of the alveoli and tissues in the lung, whereas elastic work refers to the work of the intercostal muscles, chest wall, and
diaphragm. Increasing the respiration rate increases the flow-resistive work of the airways and decreases the elastic work of
the muscles. Decreasing the respiratory rate reverses the type of work required.
Surfactant
The air-tissue/water interface of the alveoli has a high surface tension. This surface tension is similar to the surface tension
of water at the liquid-air interface of a water droplet that results in the bonding of the water molecules together. Surfactant
is a complex mixture of phospholipids and lipoproteins that works to reduce the surface tension that exists between the
alveoli tissue and the air found within the alveoli. By lowering the surface tension of the alveolar fluid, it reduces the
tendency of alveoli to collapse.
Surfactant works like a detergent to reduce the surface tension and allows for easier inflation of the airways. When a balloon
is first inflated, it takes a large amount of effort to stretch the plastic and start to inflate the balloon. If a little bit of detergent
was applied to the interior of the balloon, then the amount of effort or work needed to begin to inflate the balloon would
decrease, and it would become much easier to start blowing up the balloon. This same principle applies to the airways. A
small amount of surfactant to the airway tissues reduces the effort or work needed to inflate those airways. Babies born
prematurely sometimes do not produce enough surfactant. As a result, they suffer from respiratory distress syndrome ,
because it requires more effort to inflate their lungs. Surfactant is also important for preventing collapse of small alveoli
relative to large alveoli.
Lung Resistance and Compliance
Pulmonary diseases reduce the rate of gas exchange into and out of the lungs. Two main causes of decreased gas exchange
are compliance (how elastic the lung is) and resistance (how much obstruction exists in the airways). A change in either
can dramatically alter breathing and the ability to take in oxygen and release carbon dioxide.
Examples of restrictive diseases are respiratory distress syndrome and pulmonary fibrosis. In both diseases, the airways are
less compliant and they are stiff or fibrotic. There is a decrease in compliance because the lung tissue cannot bend and move.
In these types of restrictive diseases, the intrapleural pressure is more positive and the airways collapse upon exhalation,
which traps air in the lungs. Forced or functional vital capacity (FVC) , which is the amount of air that can be forcibly
exhaled after taking the deepest breath possible, is much lower than in normal patients, and the time it takes to exhale most
of the air is greatly prolonged ( Figure 39.18 ). A patient suffering from these diseases cannot exhale the normal amount of
air.
Obstructive diseases and conditions include emphysema, asthma, and pulmonary edema. In emphysema, which mostly
arises from smoking tobacco, the walls of the alveoli are destroyed, decreasing the surface area for gas exchange. The
overall compliance of the lungs is increased, because as the alveolar walls are damaged, lung elastic recoil decreases due to a
loss of elastic fibers, and more air is trapped in the lungs at the end of exhalation. Asthma is a disease in which inflammation
is triggered by environmental factors. Inflammation obstructs the airways. The obstruction may be due to edema (fluid
accumulation), smooth muscle spasms in the walls of the bronchioles, increased mucus secretion, damage to the epithelia of
the airways, or a combination of these events. Those with asthma or edema experience increased occlusion from increased
inflammation of the airways. This tends to block the airways, preventing the proper movement of gases ( Figure 39.18 ).
Those with obstructive diseases have large volumes of air trapped after exhalation and breathe at a very high lung volume
to compensate for the lack of airway recruitment.
Chapter 39 | The Respiratory System 1151 Figure 39.18 The ratio of FEV1 (the amount of air that can be forcibly exhaled in one second after taking a deep
breath) to FVC (the total amount of air that can be forcibly exhaled) can be used to diagnose whether a person has
restrictive or obstructive lung disease. In restrictive lung disease, FVC is reduced but airways are not obstructed, so
the person is able to expel air reasonably fast. In obstructive lung disease, airway obstruction results in slow exhalation
as well as reduced FVC. Thus, the FEV1/FVC ratio is lower in persons with obstructive lung disease (less than 69
percent) than in persons with restrictive disease (88 to 90 percent).
Dead Space: V/Q Mismatch
Pulmonary circulation pressure is very low compared to that of the systemic circulation. It is also independent of cardiac
output. This is because of a phenomenon called recruitment , which is the process of opening airways that normally remain
closed when cardiac output increases. As cardiac output increases, the number of capillaries and arteries that are perfused
(filled with blood) increases. These capillaries and arteries are not always in use but are ready if needed. At times, however,
there is a mismatch between the amount of air (ventilation, V) and the amount of blood (perfusion, Q) in the lungs. This is
referred to as ventilation/perfusion (V/Q) mismatch .
There are two types of V/Q mismatch. Both produce dead space , regions of broken down or blocked lung tissue. Dead
spaces can severely impact breathing, because they reduce the surface area available for gas diffusion. As a result, the
amount of oxygen in the blood decreases, whereas the carbon dioxide level increases. Dead space is created when no
ventilation and/or perfusion takes place. Anatomical dead space or anatomical shunt, arises from an anatomical failure,
while physiological dead space or physiological shunt, arises from a functional impairment of the lung or arteries.
An example of an anatomical shunt is the effect of gravity on the lungs. The lung is particularly susceptible to changes in the
magnitude and direction of gravitational forces. When someone is standing or sitting upright, the pleural pressure gradient
leads to increased ventilation further down in the lung. As a result, the intrapleural pressure is more negative at the base
of the lung than at the top, and more air fills the bottom of the lung than the top. Likewise, it takes less energy to pump
blood to the bottom of the lung than to the top when in a prone position. Perfusion of the lung is not uniform while standing
or sitting. This is a result of hydrostatic forces combined with the effect of airway pressure. An anatomical shunt develops
because the ventilation of the airways does not match the perfusion of the arteries surrounding those airways. As a result,
the rate of gas exchange is reduced. Note that this does not occur when lying down, because in this position, gravity does
not preferentially pull the bottom of the lung down.
A physiological shunt can develop if there is infection or edema in the lung that obstructs an area. This will decrease
ventilation but not affect perfusion; therefore, the V/Q ratio changes and gas exchange is affected.
The lung can compensate for these mismatches in ventilation and perfusion. If ventilation is greater than perfusion, the
arterioles dilate and the bronchioles constrict. This increases perfusion and reduces ventilation. Likewise, if ventilation is
less than perfusion, the arterioles constrict and the bronchioles dilate to correct the imbalance.
1152 Chapter 39 | The Respiratory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Visit this site (http://openstaxcollege.org/l/breathing) to view the mechanics of breathing.
39.4 | Transport of Gases in Human Bodily Fluids
By the end of this section, you will be able to:
• Describe how oxygen is bound to hemoglobin and transported to body tissues
• Explain how carbon dioxide is transported from body tissues to the lungs
Once the oxygen diffuses across the alveoli, it enters the bloodstream and is transported to the tissues where it is unloaded,
and carbon dioxide diffuses out of the blood and into the alveoli to be expelled from the body. Although gas exchange is a
continuous process, the oxygen and carbon dioxide are transported by different mechanisms.
Transport of Oxygen in the Blood
Although oxygen dissolves in blood, only a small amount of oxygen is transported this way. Only 1.5 percent of oxygen in
the blood is dissolved directly into the blood itself. Most oxygen—98.5 percent—is bound to a protein called hemoglobin
and carried to the tissues.
Hemoglobin
Hemoglobin , or Hb, is a protein molecule found in red blood cells (erythrocytes) made of four subunits: two alpha subunits
and two beta subunits ( Figure 39.19 ). Each subunit surrounds a central heme group that contains iron and binds one oxygen
molecule, allowing each hemoglobin molecule to bind four oxygen molecules. Molecules with more oxygen bound to the
heme groups are brighter red. As a result, oxygenated arterial blood where the Hb is carrying four oxygen molecules is
bright red, while venous blood that is deoxygenated is darker red.
Figure 39.19 The protein inside (a) red blood cells that carries oxygen to cells and carbon dioxide to the lungs is (b)
hemoglobin. Hemoglobin is made up of four symmetrical subunits and four heme groups. Iron associated with the
heme binds oxygen. It is the iron in hemoglobin that gives blood its red color.
It is easier to bind a second and third oxygen molecule to Hb than the first molecule. This is because the hemoglobin
molecule changes its shape, or conformation, as oxygen binds. The fourth oxygen is then more difficult to bind. The binding
of oxygen to hemoglobin can be plotted as a function of the partial pressure of oxygen in the blood (x-axis) versus the
Chapter 39 | The Respiratory System 1153 relative Hb-oxygen saturation (y-axis). The resulting graph—an oxygen dissociation curve —is sigmoidal, or S-shaped
(Figure 39.20 ). As the partial pressure of oxygen increases, the hemoglobin becomes increasingly saturated with oxygen.
Figure 39.20 The oxygen dissociation curve demonstrates that, as the partial pressure of oxygen increases,
more oxygen binds hemoglobin. However, the affinity of hemoglobin for oxygen may shift to the left or the right
depending on environmental conditions.
The kidneys are responsible for removing excess H+ ions from the blood. If the kidneys fail, what would
happen to blood pH and to hemoglobin affinity for oxygen?
Factors That Affect Oxygen Binding
The oxygen-carrying capacity of hemoglobin determines how much oxygen is carried in the blood. In addition to PO2,
other environmental factors and diseases can affect oxygen carrying capacity and delivery.
Carbon dioxide levels, blood pH, and body temperature affect oxygen-carrying capacity ( Figure 39.20 ). When carbon
dioxide is in the blood, it reacts with water to form bicarbonate (HCO 3− )and hydrogen ions (H +). As the level of carbon
dioxide in the blood increases, more H +is produced and the pH decreases. This increase in carbon dioxide and subsequent
decrease in pH reduce the affinity of hemoglobin for oxygen. The oxygen dissociates from the Hb molecule, shifting the
oxygen dissociation curve to the right. Therefore, more oxygen is needed to reach the same hemoglobin saturation level
as when the pH was higher. A similar shift in the curve also results from an increase in body temperature. Increased
temperature, such as from increased activity of skeletal muscle, causes the affinity of hemoglobin for oxygen to be reduced.
Diseases like sickle cell anemia and thalassemia decrease the blood’s ability to deliver oxygen to tissues and its oxygen-
carrying capacity. In sickle cell anemia , the shape of the red blood cell is crescent-shaped, elongated, and stiffened,
reducing its ability to deliver oxygen ( Figure 39.21 ). In this form, red blood cells cannot pass through the capillaries. This
is painful when it occurs. Thalassemia is a rare genetic disease caused by a defect in either the alpha or the beta subunit
of Hb. Patients with thalassemia produce a high number of red blood cells, but these cells have lower-than-normal levels of
hemoglobin. Therefore, the oxygen-carrying capacity is diminished.
1154 Chapter 39 | The Respiratory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 39.21 Individuals with sickle cell anemia have crescent-shaped red blood cells. (credit: modification of work by
Ed Uthman; scale-bar data from Matt Russell)
Transport of Carbon Dioxide in the Blood
Carbon dioxide molecules are transported in the blood from body tissues to the lungs by one of three methods: dissolution
directly into the blood, binding to hemoglobin, or carried as a bicarbonate ion. Several properties of carbon dioxide in the
blood affect its transport. First, carbon dioxide is more soluble in blood than oxygen. About 5 to 7 percent of all carbon
dioxide is dissolved in the plasma. Second, carbon dioxide can bind to plasma proteins or can enter red blood cells and bind
to hemoglobin. This form transports about 10 percent of the carbon dioxide. When carbon dioxide binds to hemoglobin, a
molecule called carbaminohemoglobin is formed. Binding of carbon dioxide to hemoglobin is reversible. Therefore, when
it reaches the lungs, the carbon dioxide can freely dissociate from the hemoglobin and be expelled from the body.
Third, the majority of carbon dioxide molecules (85 percent) are carried as part of the bicarbonate buffer system .
In this system, carbon dioxide diffuses into the red blood cells. Carbonic anhydrase (CA) within the red blood cells
quickly converts the carbon dioxide into carbonic acid (H 2CO 3). Carbonic acid is an unstable intermediate molecule
that immediately dissociates into bicarbonate ions (HCO 3− )and hydrogen (H +) ions. Since carbon dioxide is quickly
converted into bicarbonate ions, this reaction allows for the continued uptake of carbon dioxide into the blood down its
concentration gradient. It also results in the production of H +ions. If too much H +is produced, it can alter blood pH.
However, hemoglobin binds to the free H +ions and thus limits shifts in pH. The newly synthesized bicarbonate ion is
transported out of the red blood cell into the liquid component of the blood in exchange for a chloride ion (Cl -); this is
called the chloride shift . When the blood reaches the lungs, the bicarbonate ion is transported back into the red blood cell in
exchange for the chloride ion. The H +ion dissociates from the hemoglobin and binds to the bicarbonate ion. This produces
the carbonic acid intermediate, which is converted back into carbon dioxide through the enzymatic action of CA. The carbon
dioxide produced is expelled through the lungs during exhalation.
CO 2 + H 2O↔ H2CO 3
(carbonic acid) ↔ HCO 3 + H +
(bicarbonate)
The benefit of the bicarbonate buffer system is that carbon dioxide is “soaked up” into the blood with little change to the pH
of the system. This is important because it takes only a small change in the overall pH of the body for severe injury or death
to result. The presence of this bicarbonate buffer system also allows for people to travel and live at high altitudes: When
the partial pressure of oxygen and carbon dioxide change at high altitudes, the bicarbonate buffer system adjusts to regulate
carbon dioxide while maintaining the correct pH in the body.
Carbon Monoxide Poisoning
While carbon dioxide can readily associate and dissociate from hemoglobin, other molecules such as carbon monoxide (CO)
cannot. Carbon monoxide has a greater affinity for hemoglobin than oxygen. Therefore, when carbon monoxide is present,
it binds to hemoglobin preferentially over oxygen. As a result, oxygen cannot bind to hemoglobin, so very little oxygen
is transported through the body ( Figure 39.22 ). Carbon monoxide is a colorless, odorless gas and is therefore difficult to
detect. It is produced by gas-powered vehicles and tools. Carbon monoxide can cause headaches, confusion, and nausea;
long-term exposure can cause brain damage or death. Administering 100 percent (pure) oxygen is the usual treatment for
carbon monoxide poisoning. Administration of pure oxygen speeds up the separation of carbon monoxide from hemoglobin.
Chapter 39 | The Respiratory System 1155 Figure 39.22 As percent CO increases, the oxygen saturation of hemoglobin decreases.
1156 Chapter 39 | The Respiratory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 alveolar PO2
alveolar duct
alveolar sac
alveolar ventilation
alveolus
anatomical dead space
bicarbonate (HCO 3− )ion
bicarbonate buffer system
bronchiole
bronchus
carbaminohemoglobin
carbonic anhydrase (CA)
chloride shift
compliance
dead space
diaphragm
elastic recoil
elastic work
expiratory reserve volume (ERV)
FEV1/FVC ratio
flow-resistive
forced expiratory volume (FEV)
functional residual capacity (FRC)
functional vital capacity (FVC)
heme group
hemoglobin
inspiratory capacity (IC)
inspiratory reserve volume (IRV)
KEY TERMS
partial pressure of oxygen in the alveoli (usually around 100 mmHg)
duct that extends from the terminal bronchiole to the alveolar sac
structure consisting of two or more alveoli that share a common opening
how much air is in the alveoli
(plural: alveoli) (also, air sac) terminal region of the lung where gas exchange occurs
(also, anatomical shunt) region of the lung that lacks proper ventilation/perfusion due to an
anatomical block
ion created when carbonic acid dissociates into H +and (HCO 3− )
system in the blood that absorbs carbon dioxide and regulates pH levels
airway that extends from the main tertiary bronchi to the alveolar sac
(plural: bronchi) smaller branch of cartilaginous tissue that stems off of the trachea; air is funneled through the
bronchi to the region where gas exchange occurs in alveoli
molecule that forms when carbon dioxide binds to hemoglobin
enzyme that catalyzes carbon dioxide and water into carbonic acid
chloride shift exchange of chloride for bicarbonate into or out of the red blood cell
measurement of the elasticity of the lung
area in the lung that lacks proper ventilation or perfusion
domed-shaped skeletal muscle located under lungs that separates the thoracic cavity from the abdominal
cavity
property of the lung that drives the lung tissue inward
work conducted by the intercostal muscles, chest wall, and diaphragm
amount of additional air that can be exhaled after a normal exhalation
ratio of how much air can be forced out of the lung in one second to the total amount that is forced out of
the lung; a measurement of lung function that can be used to detect disease states
work of breathing performed by the alveoli and tissues in the lung
(also, forced vital capacity) measure of how much air can be forced out of the lung
from maximal inspiration over a specific amount of time
expiratory reserve volume plus residual volume
amount of air that can be forcibly exhaled after taking the deepest breath possible
centralized iron-containing group that is surrounded by the alpha and beta subunits of hemoglobin
molecule in red blood cells that can bind oxygen, carbon dioxide, and carbon monoxide
tidal volume plus inspiratory reserve volume
amount of additional air that can be inspired after a normal inhalation
Chapter 39 | The Respiratory System 1157 intercostal muscle
intrapleural space
larynx
lung capacity
lung volume
mucin
mucus
nasal cavity
obstructive disease
oxygen dissociation curve
oxygen-carrying capacity
partial pressure
particulate matter
pharynx
physiological dead space
pleura
pleurisy
primary bronchus
recruitment
residual volume (RV)
resistance
respiratory bronchiole
respiratory distress syndrome
respiratory quotient (RQ)
respiratory rate
restrictive disease
sickle cell anemia
spirometry
muscle connected to the rib cage that contracts upon inspiration
space between the layers of pleura
voice box, a short passageway connecting the pharynx and the trachea
measurement of two or more lung volumes (how much air can be inhaled from the end of an expiration to
maximal capacity)
measurement of air for one lung function (normal inhalation or exhalation)
complex glycoprotein found in mucus
sticky protein-containing fluid secretion in the lung that traps particulate matter to be expelled from the body
opening of the respiratory system to the outside environment
disease (such as emphysema and asthma) that arises from obstruction of the airways; compliance
increases in these diseases
curve depicting the affinity of oxygen for hemoglobin
amount of oxygen that can be transported in the blood
amount of pressure exerted by one gas within a mixture of gases
small particle such as dust, dirt, viral particles, and bacteria that are in the air
throat; a tube that starts in the internal nares and runs partway down the neck, where it opens into the esophagus
and the larynx
(also, physiological shunt) region of the lung that lacks proper ventilation/perfusion due to a
physiological change in the lung (like inflammation or edema)
tissue layer that surrounds the lungs and lines the interior of the thoracic cavity
painful inflammation of the pleural tissue layers
(also, main bronchus) region of the airway within the lung that attaches to the trachea and bifurcates
to each lung where it branches into secondary bronchi
process of opening airways that normally remain closed when the cardiac output increases
amount of air remaining in the lung after a maximal expiration
measurement of lung obstruction
terminal portion of the bronchiole tree that is attached to the terminal bronchioles and alveoli
ducts, alveolar sacs, and alveoli
disease that arises from a deficient amount of surfactant
ratio of carbon dioxide production to each oxygen molecule consumed
number of breaths per minute
disease that results from a restriction and decreased compliance of the alveoli; respiratory distress
syndrome and pulmonary fibrosis are examples
genetic disorder that affects the shape of red blood cells, and their ability to transport oxygen and
move through capillaries
method to measure lung volumes and to diagnose lung diseases
1158 Chapter 39 | The Respiratory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 surfactant
terminal bronchiole
thalassemia
tidal volume (TV)
total lung capacity (TLC)
trachea
venous PCO 2
venous PO2
ventilation/perfusion (V/Q) mismatch
vital capacity (VC)
detergent-like liquid in the airways that lowers the surface tension of the alveoli to allow for expansion
region of bronchiole that attaches to the respiratory bronchioles
rare genetic disorder that results in mutation of the alpha or beta subunits of hemoglobin, creating smaller
red blood cells with less hemoglobin
amount of air that is inspired and expired during normal breathing
sum of the residual volume, expiratory reserve volume, tidal volume, and inspiratory reserve
volume
cartilaginous tube that transports air from the larynx to the primary bronchi
partial pressure of carbon dioxide in the veins (40 mm Hg in the pulmonary veins)
partial pressure of oxygen in the veins (100 mm Hg in the pulmonary veins)
region of the lung that lacks proper alveolar ventilation (V) and/or arterial
perfusion (Q)
sum of the expiratory reserve volume, tidal volume, and inspiratory reserve volume
CHAPTER SUMMARY
39.1 Systems of Gas Exchange
Animal respiratory systems are designed to facilitate gas exchange. In mammals, air is warmed and humidified in the nasal
cavity. Air then travels down the pharynx, through the trachea, and into the lungs. In the lungs, air passes through the
branching bronchi, reaching the respiratory bronchioles, which house the first site of gas exchange. The respiratory
bronchioles open into the alveolar ducts, alveolar sacs, and alveoli. Because there are so many alveoli and alveolar sacs in
the lung, the surface area for gas exchange is very large. Several protective mechanisms are in place to prevent damage or
infection. These include the hair and mucus in the nasal cavity that trap dust, dirt, and other particulate matter before they
can enter the system. In the lungs, particles are trapped in a mucus layer and transported via cilia up to the esophageal
opening at the top of the trachea to be swallowed.
39.2 Gas Exchange across Respiratory Surfaces
The lungs can hold a large volume of air, but they are not usually filled to maximal capacity. Lung volume measurements
include tidal volume, expiratory reserve volume, inspiratory reserve volume, and residual volume. The sum of these equals
the total lung capacity. Gas movement into or out of the lungs is dependent on the pressure of the gas. Air is a mixture of
gases; therefore, the partial pressure of each gas can be calculated to determine how the gas will flow in the lung. The
difference between the partial pressure of the gas in the air drives oxygen into the tissues and carbon dioxide out of the
body.
39.3 Breathing
The structure of the lungs and thoracic cavity control the mechanics of breathing. Upon inspiration, the diaphragm
contracts and lowers. The intercostal muscles contract and expand the chest wall outward. The intrapleural pressure drops,
the lungs expand, and air is drawn into the airways. When exhaling, the intercostal muscles and diaphragm relax, returning
the intrapleural pressure back to the resting state. The lungs recoil and airways close. The air passively exits the lung.
There is high surface tension at the air-airway interface in the lung. Surfactant, a mixture of phospholipids and
lipoproteins, acts like a detergent in the airways to reduce surface tension and allow for opening of the alveoli.
Breathing and gas exchange are both altered by changes in the compliance and resistance of the lung. If the compliance of
the lung decreases, as occurs in restrictive diseases like fibrosis, the airways stiffen and collapse upon exhalation. Air
becomes trapped in the lungs, making breathing more difficult. If resistance increases, as happens with asthma or
emphysema, the airways become obstructed, trapping air in the lungs and causing breathing to become difficult.
Alterations in the ventilation of the airways or perfusion of the arteries can affect gas exchange. These changes in
ventilation and perfusion, called V/Q mismatch, can arise from anatomical or physiological changes.
Chapter 39 | The Respiratory System 1159 39.4 Transport of Gases in Human Bodily Fluids
Hemoglobin is a protein found in red blood cells that is comprised of two alpha and two beta subunits that surround an
iron-containing heme group. Oxygen readily binds this heme group. The ability of oxygen to bind increases as more
oxygen molecules are bound to heme. Disease states and altered conditions in the body can affect the binding ability of
oxygen, and increase or decrease its ability to dissociate from hemoglobin.
Carbon dioxide can be transported through the blood via three methods. It is dissolved directly in the blood, bound to
plasma proteins or hemoglobin, or converted into bicarbonate. The majority of carbon dioxide is transported as part of the
bicarbonate system. Carbon dioxide diffuses into red blood cells. Inside, carbonic anhydrase converts carbon dioxide into
carbonic acid (H 2CO 3), which is subsequently hydrolyzed into bicarbonate (HCO 3− )and H +. The H +ion binds to
hemoglobin in red blood cells, and bicarbonate is transported out of the red blood cells in exchange for a chloride ion. This
is called the chloride shift. Bicarbonate leaves the red blood cells and enters the blood plasma. In the lungs, bicarbonate is
transported back into the red blood cells in exchange for chloride. The H +dissociates from hemoglobin and combines with
bicarbonate to form carbonic acid with the help of carbonic anhydrase, which further catalyzes the reaction to convert
carbonic acid back into carbon dioxide and water. The carbon dioxide is then expelled from the lungs.
ART CONNECTION QUESTIONS
1. Figure 39.7 Which of the following statements about
the mammalian respiratory system is false?
a. When we breathe in, air travels from the
pharynx to the trachea.
b. The bronchioles branch into bronchi.
c. Alveolar ducts connect to alveolar sacs.
d. Gas exchange between the lung and blood takes
place in the alveolus.
2. Figure 39.13 Which of the following statements is
false?
a. In the tissues, PO2drops as blood passes from
the arteries to the veins, while PCO 2increases.
b. Blood travels from the lungs to the heart to body
tissues, then back to the heart, then the lungs.
c. Blood travels from the lungs to the heart to body
tissues, then back to the lungs, then the heart.
d. PO2is higher in air than in the lungs.
3. Figure 39.20 The kidneys are responsible for removing
excess H+ ions from the blood. If the kidneys fail, what
would happen to blood pH and to hemoglobin affinity for
oxygen?
REVIEW QUESTIONS
4. The respiratory system ________.
a. provides body tissues with oxygen
b. provides body tissues with oxygen and carbon
dioxide
c. establishes how many breaths are taken per
minute
d. provides the body with carbon dioxide
5. Air is warmed and humidified in the nasal passages.
This helps to ________.
a. ward off infection
b. decrease sensitivity during breathing
c. prevent damage to the lungs
d. all of the above
6. Which is the order of airflow during inhalation?
a. nasal cavity, trachea, larynx, bronchi,
bronchioles, alveoli
b. nasal cavity, larynx, trachea, bronchi,
bronchioles, alveoli
c. nasal cavity, larynx, trachea, bronchioles,
bronchi, alveoli
d. nasal cavity, trachea, larynx, bronchi,
bronchioles, alveoli
7. The inspiratory reserve volume measures the ________.
a. amount of air remaining in the lung after a
maximal exhalation
b. amount of air that the lung holds
c. amount of air the can be further exhaled after a
normal breath
d. amount of air that can be further inhaled after a
normal breath
8. Of the following, which does not explain why the
partial pressure of oxygen is lower in the lung than in the
external air?
a. Air in the lung is humidified; therefore, water
vapor pressure alters the pressure.
b. Carbon dioxide mixes with oxygen.
c. Oxygen is moved into the blood and is headed to
the tissues.
d. Lungs exert a pressure on the air to reduce the
oxygen pressure.
1160 Chapter 39 | The Respiratory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 9. The total lung capacity is calculated using which of the
following formulas?
a. residual volume + tidal volume + inspiratory
reserve volume
b. residual volume + expiratory reserve volume +
inspiratory reserve volume
c. expiratory reserve volume + tidal volume +
inspiratory reserve volume
d. residual volume + expiratory reserve volume +
tidal volume + inspiratory reserve volume
10. How would paralysis of the diaphragm alter
inspiration?
a. It would prevent contraction of the intercostal
muscles.
b. It would prevent inhalation because the
intrapleural pressure would not change.
c. It would decrease the intrapleural pressure and
allow more air to enter the lungs.
d. It would slow expiration because the lung would
not relax.
11. Restrictive airway diseases ________.
a. increase the compliance of the lung
b. decrease the compliance of the lung
c. increase the lung volume
d. decrease the work of breathing
12. Alveolar ventilation remains constant when ________.
a. the respiratory rate is increased while the
volume of air per breath is decreased
b. the respiratory rate and the volume of air per
breath are increased
c. the respiratory rate is decreased while increasing
the volume per breath
d. both a and c
13. Which of the following will NOT facilitate the transfer
of oxygen to tissues?
a. decreased body temperature
b. decreased pH of the blood
c. increased carbon dioxide
d. increased exercise
14. The majority of carbon dioxide in the blood is
transported by ________.
a. binding to hemoglobin
b. dissolution in the blood
c. conversion to bicarbonate
d. binding to plasma proteins
15. The majority of oxygen in the blood is transported by
________.
a. dissolution in the blood
b. being carried as bicarbonate ions
c. binding to blood plasma
d. binding to hemoglobin
CRITICAL THINKING QUESTIONS
16. Describe the function of these terms and describe
where they are located: main bronchus, trachea, alveoli,
and acinus.
17. How does the structure of alveoli maximize gas
exchange?
18. What does FEV1/FVC measure? What factors may
affect FEV1/FVC?
19. What is the reason for having residual volume in the
lung?
20. How can a decrease in the percent of oxygen in the air
affect the movement of oxygen in the body?
21. If a patient has increased resistance in his or her lungs,
how can this detected by a doctor? What does this mean?
22. How would increased airway resistance affect
intrapleural pressure during inhalation?
23. Explain how a puncture to the thoracic cavity (from a
knife wound, for instance) could alter the ability to inhale.
24. When someone is standing, gravity stretches the
bottom of the lung down toward the floor to a greater
extent than the top of the lung. What implication could this
have on the flow of air in the lungs? Where does gas
exchange occur in the lungs?
25. What would happen if no carbonic anhydrase were
present in red blood cells?
26. How does the administration of 100 percent oxygen
save a patient from carbon monoxide poisoning? Why
wouldn’t giving carbon dioxide work?
Chapter 39 | The Respiratory System 1161 1162 Chapter 39 | The Respiratory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 40 | THE CIRCULATORY
SYSTEM
Figure 40.1 Just as highway systems transport people and goods through a complex network, the circulatory system
transports nutrients, gases, and wastes throughout the animal body. (credit: modification of work by Andrey Belenko)
Chapter Outline
40.1: Overview of the Circulatory System
40.2: Components of the Blood
40.3: Mammalian Heart and Blood Vessels
40.4: Blood Flow and Blood Pressure Regulation
Introduction
Most animals are complex multicellular organisms that require a mechanism for transporting nutrients throughout their
bodies and removing waste products. The circulatory system has evolved over time from simple diffusion through cells in
the early evolution of animals to a complex network of blood vessels that reach all parts of the human body. This extensive
network supplies the cells, tissues, and organs with oxygen and nutrients, and removes carbon dioxide and waste, which are
byproducts of respiration.
At the core of the human circulatory system is the heart. The size of a clenched fist, the human heart is protected beneath
the rib cage. Made of specialized and unique cardiac muscle, it pumps blood throughout the body and to the heart itself.
Heart contractions are driven by intrinsic electrical impulses that the brain and endocrine hormones help to regulate.
Understanding the heart’s basic anatomy and function is important to understanding the body’s circulatory and respiratory
systems.
Gas exchange is one essential function of the circulatory system. A circulatory system is not needed in organisms with
no specialized respiratory organs because oxygen and carbon dioxide diffuse directly between their body tissues and
the external environment. However, in organisms that possess lungs and gills, oxygen must be transported from these
specialized respiratory organs to the body tissues via a circulatory system. Therefore, circulatory systems have had to evolve
to accommodate the great diversity of body sizes and body types present among animals.
Chapter 40 | The Circulatory System 1163 40.1 | Overview of the Circulatory System
By the end of this section, you will be able to:
• Describe an open and closed circulatory system
• Describe interstitial fluid and hemolymph
• Compare and contrast the organization and evolution of the vertebrate circulatory system.
In all animals, except a few simple types, the circulatory system is used to transport nutrients and gases through the body.
Simple diffusion allows some water, nutrient, waste, and gas exchange into primitive animals that are only a few cell layers
thick; however, bulk flow is the only method by which the entire body of larger more complex organisms is accessed.
Circulatory System Architecture
The circulatory system is effectively a network of cylindrical vessels: the arteries, veins, and capillaries that emanate from a
pump, the heart. In all vertebrate organisms, as well as some invertebrates, this is a closed-loop system, in which the blood is
not free in a cavity. In a closed circulatory system , blood is contained inside blood vessels and circulates unidirectionally
from the heart around the systemic circulatory route, then returns to the heart again, as illustrated in Figure 40.2 a. As
opposed to a closed system, arthropods—including insects, crustaceans, and most mollusks—have an open circulatory
system, as illustrated in Figure 40.2 b. In an open circulatory system , the blood is not enclosed in the blood vessels but is
pumped into a cavity called a hemocoel and is called hemolymph because the blood mixes with the interstitial fluid . As
the heart beats and the animal moves, the hemolymph circulates around the organs within the body cavity and then reenters
the hearts through openings called ostia . This movement allows for gas and nutrient exchange. An open circulatory system
does not use as much energy as a closed system to operate or to maintain; however, there is a trade-off with the amount of
blood that can be moved to metabolically active organs and tissues that require high levels of oxygen. In fact, one reason
that insects with wing spans of up to two feet wide (70 cm) are not around today is probably because they were outcompeted
by the arrival of birds 150 million years ago. Birds, having a closed circulatory system, are thought to have moved more
agilely, allowing them to get food faster and possibly to prey on the insects.
Figure 40.2 In (a) closed circulatory systems, the heart pumps blood through vessels that are separate from the
interstitial fluid of the body. Most vertebrates and some invertebrates, like this annelid earthworm, have a closed
circulatory system. In (b) open circulatory systems, a fluid called hemolymph is pumped through a blood vessel that
empties into the body cavity. Hemolymph returns to the blood vessel through openings called ostia. Arthropods like
this bee and most mollusks have open circulatory systems.
Circulatory System Variation in Animals
The circulatory system varies from simple systems in invertebrates to more complex systems in vertebrates. The simplest
animals, such as the sponges (Porifera) and rotifers (Rotifera), do not need a circulatory system because diffusion allows
adequate exchange of water, nutrients, and waste, as well as dissolved gases, as shown in Figure 40.3 a. Organisms that
are more complex but still only have two layers of cells in their body plan, such as jellies (Cnidaria) and comb jellies
(Ctenophora) also use diffusion through their epidermis and internally through the gastrovascular compartment. Both their
internal and external tissues are bathed in an aqueous environment and exchange fluids by diffusion on both sides, as
illustrated in Figure 40.3 b. Exchange of fluids is assisted by the pulsing of the jellyfish body.
1164 Chapter 40 | The Circulatory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 40.3 Simple animals consisting of a single cell layer such as the (a) sponge or only a few cell layers such as
the (b) jellyfish do not have a circulatory system. Instead, gases, nutrients, and wastes are exchanged by diffusion.
For more complex organisms, diffusion is not efficient for cycling gases, nutrients, and waste effectively through the
body; therefore, more complex circulatory systems evolved. Most arthropods and many mollusks have open circulatory
systems. In an open system, an elongated beating heart pushes the hemolymph through the body and muscle contractions
help to move fluids. The larger more complex crustaceans, including lobsters, have developed arterial-like vessels to push
blood through their bodies, and the most active mollusks, such as squids, have evolved a closed circulatory system and
are able to move rapidly to catch prey. Closed circulatory systems are a characteristic of vertebrates; however, there are
significant differences in the structure of the heart and the circulation of blood between the different vertebrate groups due
to adaptation during evolution and associated differences in anatomy. Figure 40.4 illustrates the basic circulatory systems
of some vertebrates: fish, amphibians, reptiles, and mammals.
Chapter 40 | The Circulatory System 1165 Figure 40.4 (a) Fish have the simplest circulatory systems of the vertebrates: blood flows unidirectionally from the two-
chambered heart through the gills and then the rest of the body. (b) Amphibians have two circulatory routes: one for
oxygenation of the blood through the lungs and skin, and the other to take oxygen to the rest of the body. The blood
is pumped from a three-chambered heart with two atria and a single ventricle. (c) Reptiles also have two circulatory
routes; however, blood is only oxygenated through the lungs. The heart is three chambered, but the ventricles are
partially separated so some mixing of oxygenated and deoxygenated blood occurs except in crocodilians and birds.
(d) Mammals and birds have the most efficient heart with four chambers that completely separate the oxygenated and
deoxygenated blood; it pumps only oxygenated blood through the body and deoxygenated blood to the lungs.
As illustrated in Figure 40.4 aFish have a single circuit for blood flow and a two-chambered heart that has only a single
atrium and a single ventricle. The atrium collects blood that has returned from the body and the ventricle pumps the blood to
the gills where gas exchange occurs and the blood is re-oxygenated; this is called gill circulation . The blood then continues
through the rest of the body before arriving back at the atrium; this is called systemic circulation . This unidirectional flow
of blood produces a gradient of oxygenated to deoxygenated blood around the fish’s systemic circuit. The result is a limit in
the amount of oxygen that can reach some of the organs and tissues of the body, reducing the overall metabolic capacity of
fish.
1166 Chapter 40 | The Circulatory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 In amphibians, reptiles, birds, and mammals, blood flow is directed in two circuits: one through the lungs and back to the
heart, which is called pulmonary circulation , and the other throughout the rest of the body and its organs including the
brain (systemic circulation). In amphibians, gas exchange also occurs through the skin during pulmonary circulation and is
referred to as pulmocutaneous circulation .
As shown in Figure 40.4 b, amphibians have a three-chambered heart that has two atria and one ventricle rather than the
two-chambered heart of fish. The two atria (superior heart chambers) receive blood from the two different circuits (the
lungs and the systems), and then there is some mixing of the blood in the heart’s ventricle (inferior heart chamber), which
reduces the efficiency of oxygenation. The advantage to this arrangement is that high pressure in the vessels pushes blood
to the lungs and body. The mixing is mitigated by a ridge within the ventricle that diverts oxygen-rich blood through the
systemic circulatory system and deoxygenated blood to the pulmocutaneous circuit. For this reason, amphibians are often
described as having double circulation .
Most reptiles also have a three-chambered heart similar to the amphibian heart that directs blood to the pulmonary and
systemic circuits, as shown in Figure 40.4 c. The ventricle is divided more effectively by a partial septum, which results in
less mixing of oxygenated and deoxygenated blood. Some reptiles (alligators and crocodiles) are the most primitive animals
to exhibit a four-chambered heart. Crocodilians have a unique circulatory mechanism where the heart shunts blood from
the lungs toward the stomach and other organs during long periods of submergence, for instance, while the animal waits for
prey or stays underwater waiting for prey to rot. One adaptation includes two main arteries that leave the same part of the
heart: one takes blood to the lungs and the other provides an alternate route to the stomach and other parts of the body. Two
other adaptations include a hole in the heart between the two ventricles, called the foramen of Panizza, which allows blood
to move from one side of the heart to the other, and specialized connective tissue that slows the blood flow to the lungs.
Together these adaptations have made crocodiles and alligators one of the most evolutionarily successful animal groups on
earth.
In mammals and birds, the heart is also divided into four chambers: two atria and two ventricles, as illustrated in Figure
40.4 d. The oxygenated blood is separated from the deoxygenated blood, which improves the efficiency of double circulation
and is probably required for the warm-blooded lifestyle of mammals and birds. The four-chambered heart of birds and
mammals evolved independently from a three-chambered heart. The independent evolution of the same or a similar
biological trait is referred to as convergent evolution.
40.2 | Components of the Blood
By the end of this section, you will be able to:
• List the basic components of the blood
• Compare red and white blood cells
• Describe blood plasma and serum
Hemoglobin is responsible for distributing oxygen, and to a lesser extent, carbon dioxide, throughout the circulatory systems
of humans, vertebrates, and many invertebrates. The blood is more than the proteins, though. Blood is actually a term
used to describe the liquid that moves through the vessels and includes plasma (the liquid portion, which contains water,
proteins, salts, lipids, and glucose) and the cells (red and white cells) and cell fragments called platelets . Blood plasma
is actually the dominant component of blood and contains the water, proteins, electrolytes, lipids, and glucose. The cells
are responsible for carrying the gases (red cells) and immune the response (white). The platelets are responsible for blood
clotting. Interstitial fluid that surrounds cells is separate from the blood, but in hemolymph, they are combined. In humans,
cellular components make up approximately 45 percent of the blood and the liquid plasma 55 percent. Blood is 20 percent
of a person’s extracellular fluid and eight percent of weight.
The Role of Blood in the Body
Blood, like the human blood illustrated in Figure 40.5 is important for regulation of the body’s systems and homeostasis.
Blood helps maintain homeostasis by stabilizing pH, temperature, osmotic pressure, and by eliminating excess heat.
Blood supports growth by distributing nutrients and hormones, and by removing waste. Blood plays a protective role by
transporting clotting factors and platelets to prevent blood loss and transporting the disease-fighting agents or white blood
cells to sites of infection.
Chapter 40 | The Circulatory System 1167 Figure 40.5 The cells and cellular components of human blood are shown. Red blood cells deliver oxygen to the
cells and remove carbon dioxide. White blood cells—including neutrophils, monocytes, lymphocytes, eosinophils, and
basophils—are involved in the immune response. Platelets form clots that prevent blood loss after injury.
Red Blood Cells
Red blood cells , or erythrocytes (erythro- = “red”; -cyte = “cell”), are specialized cells that circulate through the body
delivering oxygen to cells; they are formed from stem cells in the bone marrow. In mammals, red blood cells are small
biconcave cells that at maturity do not contain a nucleus or mitochondria and are only 7–8 µm in size. In birds and non-
avian reptiles, a nucleus is still maintained in red blood cells.
The red coloring of blood comes from the iron-containing protein hemoglobin, illustrated in Figure 40.6 a. The principal job
of this protein is to carry oxygen, but it also transports carbon dioxide as well. Hemoglobin is packed into red blood cells at
a rate of about 250 million molecules of hemoglobin per cell. Each hemoglobin molecule binds four oxygen molecules so
that each red blood cell carries one billion molecules of oxygen. There are approximately 25 trillion red blood cells in the
five liters of blood in the human body, which could carry up to 25 sextillion (25 × 10 21) molecules of oxygen in the body at
any time. In mammals, the lack of organelles in erythrocytes leaves more room for the hemoglobin molecules, and the lack
of mitochondria also prevents use of the oxygen for metabolic respiration. Only mammals have anucleated red blood cells,
and some mammals (camels, for instance) even have nucleated red blood cells. The advantage of nucleated red blood cells
is that these cells can undergo mitosis. Anucleated red blood cells metabolize anaerobically (without oxygen), making use
of a primitive metabolic pathway to produce ATP and increase the efficiency of oxygen transport.
Not all organisms use hemoglobin as the method of oxygen transport. Invertebrates that utilize hemolymph rather than
blood use different pigments to bind to the oxygen. These pigments use copper or iron to the oxygen. Invertebrates have
a variety of other respiratory pigments. Hemocyanin, a blue-green, copper-containing protein, illustrated in Figure 40.6 b
is found in mollusks, crustaceans, and some of the arthropods. Chlorocruorin, a green-colored, iron-containing pigment is
found in four families of polychaete tubeworms. Hemerythrin, a red, iron-containing protein is found in some polychaete
worms and annelids and is illustrated in Figure 40.6 c. Despite the name, hemerythrin does not contain a heme group and
its oxygen-carrying capacity is poor compared to hemoglobin.
1168 Chapter 40 | The Circulatory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 40.6 In most vertebrates, (a) hemoglobin delivers oxygen to the body and removes some carbon dioxide.
Hemoglobin is composed of four protein subunits, two alpha chains and two beta chains, and a heme group that has
iron associated with it. The iron reversibly associates with oxygen, and in so doing is oxidized from Fe 2+ to Fe 3+.In
most mollusks and some arthropods, (b) hemocyanin delivers oxygen. Unlike hemoglobin, hemolymph is not carried in
blood cells, but floats free in the hemolymph. Copper instead of iron binds the oxygen, giving the hemolymph a blue-
green color. In annelids, such as the earthworm, and some other invertebrates, (c) hemerythrin carries oxygen. Like
hemoglobin, hemerythrin is carried in blood cells and has iron associated with it, but despite its name, hemerythrin
does not contain heme.
The small size and large surface area of red blood cells allows for rapid diffusion of oxygen and carbon dioxide across the
plasma membrane. In the lungs, carbon dioxide is released and oxygen is taken in by the blood. In the tissues, oxygen is
released from the blood and carbon dioxide is bound for transport back to the lungs. Studies have found that hemoglobin
also binds nitrous oxide (NO). NO is a vasodilator that relaxes the blood vessels and capillaries and may help with gas
exchange and the passage of red blood cells through narrow vessels. Nitroglycerin, a heart medication for angina and heart
attacks, is converted to NO to help relax the blood vessels and increase oxygen flow through the body.
A characteristic of red blood cells is their glycolipid and glycoprotein coating; these are lipids and proteins that have
carbohydrate molecules attached. In humans, the surface glycoproteins and glycolipids on red blood cells vary between
individuals, producing the different blood types, such as A, B, and O. Red blood cells have an average life span of 120 days,
at which time they are broken down and recycled in the liver and spleen by phagocytic macrophages, a type of white blood
cell.
White Blood Cells
White blood cells, also called leukocytes (leuko = white), make up approximately one percent by volume of the cells in
blood. The role of white blood cells is very different than that of red blood cells: they are primarily involved in the immune
response to identify and target pathogens, such as invading bacteria, viruses, and other foreign organisms. White blood cells
are formed continually; some only live for hours or days, but some live for years.
The morphology of white blood cells differs significantly from red blood cells. They have nuclei and do not contain
hemoglobin. The different types of white blood cells are identified by their microscopic appearance after histologic staining,
and each has a different specialized function. The two main groups, both illustrated in Figure 40.7 are the granulocytes,
which include the neutrophils, eosinophils, and basophils, and the agranulocytes, which include the monocytes and
lymphocytes.
Chapter 40 | The Circulatory System 1169 Figure 40.7 (a) Granulocytes—including neutrophils, eosinophils and basophils—are characterized by a lobed nucleus
and granular inclusions in the cytoplasm. Granulocytes are typically first-responders during injury or infection. (b)
Agranulocytes include lymphocytes and monocytes. Lymphocytes, including B and T cells, are responsible for adaptive
immune response. Monocytes differentiate into macrophages and dendritic cells, which in turn respond to infection or
injury.
Granulocytes contain granules in their cytoplasm; the agranulocytes are so named because of the lack of granules in their
cytoplasm. Some leukocytes become macrophages that either stay at the same site or move through the blood stream and
gather at sites of infection or inflammation where they are attracted by chemical signals from foreign particles and damaged
cells. Lymphocytes are the primary cells of the immune system and include B cells, T cells, and natural killer cells. B
cells destroy bacteria and inactivate their toxins. They also produce antibodies. T cells attack viruses, fungi, some bacteria,
transplanted cells, and cancer cells. T cells attack viruses by releasing toxins that kill the viruses. Natural killer cells attack
a variety of infectious microbes and certain tumor cells.
One reason that HIV poses significant management challenges is because the virus directly targets T cells by gaining entry
through a receptor. Once inside the cell, HIV then multiplies using the T cell’s own genetic machinery. After the HIV virus
replicates, it is transmitted directly from the infected T cell to macrophages. The presence of HIV can remain unrecognized
for an extensive period of time before full disease symptoms develop.
Platelets and Coagulation Factors
Blood must clot to heal wounds and prevent excess blood loss. Small cell fragments called platelets (thrombocytes) are
attracted to the wound site where they adhere by extending many projections and releasing their contents. These contents
activate other platelets and also interact with other coagulation factors, which convert fibrinogen, a water-soluble protein
present in blood serum into fibrin (a non-water soluble protein), causing the blood to clot. Many of the clotting factors
require vitamin K to work, and vitamin K deficiency can lead to problems with blood clotting. Many platelets converge and
stick together at the wound site forming a platelet plug (also called a fibrin clot), as illustrated in Figure 40.8 b. The plug or
clot lasts for a number of days and stops the loss of blood. Platelets are formed from the disintegration of larger cells called
megakaryocytes, like that shown in Figure 40.8 a. For each megakaryocyte, 2000–3000 platelets are formed with 150,000
to 400,000 platelets present in each cubic millimeter of blood. Each platelet is disc shaped and 2–4 μm in diameter. They
contain many small vesicles but do not contain a nucleus.
1170 Chapter 40 | The Circulatory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 40.8 (a) Platelets are formed from large cells called megakaryocytes. The megakaryocyte breaks up into
thousands of fragments that become platelets. (b) Platelets are required for clotting of the blood. The platelets collect
at a wound site in conjunction with other clotting factors, such as fibrinogen, to form a fibrin clot that prevents blood
loss and allows the wound to heal.
Plasma and Serum
The liquid component of blood is called plasma, and it is separated by spinning or centrifuging the blood at high rotations
(3000 rpm or higher). The blood cells and platelets are separated by centrifugal forces to the bottom of a specimen tube.
The upper liquid layer, the plasma, consists of 90 percent water along with various substances required for maintaining the
body’s pH, osmotic load, and for protecting the body. The plasma also contains the coagulation factors and antibodies.
The plasma component of blood without the coagulation factors is called the serum . Serum is similar to interstitial fluid in
which the correct composition of key ions acting as electrolytes is essential for normal functioning of muscles and nerves.
Other components in the serum include proteins that assist with maintaining pH and osmotic balance while giving viscosity
to the blood. The serum also contains antibodies, specialized proteins that are important for defense against viruses and
bacteria. Lipids, including cholesterol, are also transported in the serum, along with various other substances including
nutrients, hormones, metabolic waste, plus external substances, such as, drugs, viruses, and bacteria.
Human serum albumin is the most abundant protein in human blood plasma and is synthesized in the liver. Albumin, which
constitutes about half of the blood serum protein, transports hormones and fatty acids, buffers pH, and maintains osmotic
pressures. Immunoglobin is a protein antibody produced in the mucosal lining and plays an important role in antibody
mediated immunity.
Chapter 40 | The Circulatory System 1171 Blood Types Related to Proteins on the Surface of the Red Blood
Cells
Red blood cells are coated in antigens made of glycolipids and glycoproteins. The composition of these
molecules is determined by genetics, which have evolved over time. In humans, the different surface
antigens are grouped into 24 different blood groups with more than 100 different antigens on each red
blood cell. The two most well known blood groups are the ABO, shown in Figure 40.9 , and Rh systems.
The surface antigens in the ABO blood group are glycolipids, called antigen A and antigen B. People with
blood type A have antigen A, those with blood type B have antigen B, those with blood type AB have both
antigens, and people with blood type O have neither antigen. Antibodies called agglutinougens are found in
the blood plasma and react with the A or B antigens, if the two are mixed. When type A and type B blood are
combined, agglutination (clumping) of the blood occurs because of antibodies in the plasma that bind with
the opposing antigen; this causes clots that coagulate in the kidney causing kidney failure. Type O blood
has neither A or B antigens, and therefore, type O blood can be given to all blood types. Type O negative
blood is the universal donor. Type AB positive blood is the universal acceptor because it has both A and B
antigen. The ABO blood groups were discovered in 1900 and 1901 by Karl Landsteiner at the University of
Vienna.
The Rh blood group was first discovered in Rhesus monkeys. Most people have the Rh antigen (Rh+) and
do not have anti-Rh antibodies in their blood. The few people who do not have the Rh antigen and are
Rh– can develop anti-Rh antibodies if exposed to Rh+ blood. This can happen after a blood transfusion
or after an Rh– woman has an Rh+ baby. The first exposure does not usually cause a reaction; however,
at the second exposure, enough antibodies have built up in the blood to produce a reaction that causes
agglutination and breakdown of red blood cells. An injection can prevent this reaction.
Figure 40.9 Human red blood cells may have either type A or B glycoproteins on their surface, both glycoproteins
combined (AB), or neither (O). The glycoproteins serve as antigens and can elicit an immune response in a person
who receives a transfusion containing unfamiliar antigens. Type O blood, which has no A or B antigens, does not
elicit an immune response when injected into a person of any blood type. Thus, O is considered the universal
donor. Persons with type AB blood can accept blood from any blood type, and type AB is considered the universal
acceptor.
Play a blood typing game on the Nobel Prize website (http://openstaxcollege.org/l/blood_typing) to solidify your
understanding of blood types.
1172 Chapter 40 | The Circulatory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 40.3 | Mammalian Heart and Blood Vessels
By the end of this section, you will be able to:
• Describe the structure of the heart and explain how cardiac muscle is different from other muscles
• Describe the cardiac cycle
• Explain the structure of arteries, veins, and capillaries, and how blood flows through the body
The heart is a complex muscle that pumps blood through the three divisions of the circulatory system: the coronary (vessels
that serve the heart), pulmonary (heart and lungs), and systemic (systems of the body), as shown in Figure 40.10 . Coronary
circulation intrinsic to the heart takes blood directly from the main artery (aorta) coming from the heart. For pulmonary and
systemic circulation, the heart has to pump blood to the lungs or the rest of the body, respectively. In vertebrates, the lungs
are relatively close to the heart in the thoracic cavity. The shorter distance to pump means that the muscle wall on the right
side of the heart is not as thick as the left side which must have enough pressure to pump blood all the way to your big toe.
Figure 40.10 The mammalian circulatory system is divided into three circuits: the systemic circuit, the pulmonary
circuit, and the coronary circuit. Blood is pumped from veins of the systemic circuit into the right atrium of the
heart, then into the right ventricle. Blood then enters the pulmonary circuit, and is oxygenated by the lungs. From
the pulmonary circuit, blood re-enters the heart through the left atrium. From the left ventricle, blood re-enters the
systemic circuit through the aorta and is distributed to the rest of the body. The coronary circuit, which provides
blood to the heart, is not shown.
Which of the following statements about the circulatory system is false?
a. Blood in the pulmonary vein is deoxygenated.
b. Blood in the inferior vena cava is deoxygenated.
c. Blood in the pulmonary artery is deoxygenated.
d. Blood in the aorta is oxygenated.
Chapter 40 | The Circulatory System 1173 Structure of the Heart
The heart muscle is asymmetrical as a result of the distance blood must travel in the pulmonary and systemic circuits. Since
the right side of the heart sends blood to the pulmonary circuit it is smaller than the left side which must send blood out to
the whole body in the systemic circuit, as shown in Figure 40.11 . In humans, the heart is about the size of a clenched fist; it
is divided into four chambers: two atria and two ventricles. There is one atrium and one ventricle on the right side and one
atrium and one ventricle on the left side. The atria are the chambers that receive blood, and the ventricles are the chambers
that pump blood. The right atrium receives deoxygenated blood from the superior vena cava , which drains blood from the
jugular vein that comes from the brain and from the veins that come from the arms, as well as from the inferior vena cava
which drains blood from the veins that come from the lower organs and the legs. In addition, the right atrium receives blood
from the coronary sinus which drains deoxygenated blood from the heart itself. This deoxygenated blood then passes to the
right ventricle through the atrioventricular valve or the tricuspid valve , a flap of connective tissue that opens in only one
direction to prevent the backflow of blood. The valve separating the chambers on the left side of the heart valve is called the
biscuspid or mitral valve. After it is filled, the right ventricle pumps the blood through the pulmonary arteries, by-passing
the semilunar valve (or pulmonic valve) to the lungs for re-oxygenation. After blood passes through the pulmonary arteries,
the right semilunar valves close preventing the blood from flowing backwards into the right ventricle. The left atrium then
receives the oxygen-rich blood from the lungs via the pulmonary veins. This blood passes through the bicuspid valve or
mitral valve (the atrioventricular valve on the left side of the heart) to the left ventricle where the blood is pumped out
through aorta , the major artery of the body, taking oxygenated blood to the organs and muscles of the body. Once blood
is pumped out of the left ventricle and into the aorta, the aortic semilunar valve (or aortic valve) closes preventing blood
from flowing backward into the left ventricle. This pattern of pumping is referred to as double circulation and is found in
all mammals.
1174 Chapter 40 | The Circulatory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 40.11 (a) The heart is primarily made of a thick muscle layer, called the myocardium, surrounded by
membranes. One-way valves separate the four chambers. (b) Blood vessels of the coronary system, including the
coronary arteries and veins, keep the heart musculature oxygenated.
Which of the following statements about the heart is false?
a. The mitral valve separates the left ventricle from the left atrium.
b. Blood travels through the bicuspid valve to the left atrium.
c. Both the aortic and the pulmonary valves are semilunar valves.
d. The mitral valve is an atrioventricular valve.
The heart is composed of three layers; the epicardium, the myocardium, and the endocardium, illustrated in Figure 40.11 .
The inner wall of the heart has a lining called the endocardium . The myocardium consists of the heart muscle cells that
Chapter 40 | The Circulatory System 1175 make up the middle layer and the bulk of the heart wall. The outer layer of cells is called the epicardium , of which the
second layer is a membranous layered structure called the pericardium that surrounds and protects the heart; it allows
enough room for vigorous pumping but also keeps the heart in place to reduce friction between the heart and other
structures.
The heart has its own blood vessels that supply the heart muscle with blood. The coronary arteries branch from the aorta
and surround the outer surface of the heart like a crown. They diverge into capillaries where the heart muscle is supplied
with oxygen before converging again into the coronary veins to take the deoxygenated blood back to the right atrium
where the blood will be re-oxygenated through the pulmonary circuit. The heart muscle will die without a steady supply
of blood. Atherosclerosis is the blockage of an artery by the buildup of fatty plaques. Because of the size (narrow) of the
coronary arteries and their function in serving the heart itself, atherosclerosis can be deadly in these arteries. The slowdown
of blood flow and subsequent oxygen deprivation that results from atherosclerosis causes severe pain, known as angina , and
complete blockage of the arteries will cause myocardial infarction : the death of cardiac muscle tissue, commonly known
as a heart attack.
The Cardiac Cycle
The main purpose of the heart is to pump blood through the body; it does so in a repeating sequence called the cardiac
cycle. The cardiac cycle is the coordination of the filling and emptying of the heart of blood by electrical signals that
cause the heart muscles to contract and relax. The human heart beats over 100,000 times per day. In each cardiac cycle, the
heart contracts ( systole ), pushing out the blood and pumping it through the body; this is followed by a relaxation phase (
diastole ), where the heart fills with blood, as illustrated in Figure 40.12 . The atria contract at the same time, forcing blood
through the atrioventricular valves into the ventricles. Closing of the atrioventricular valves produces a monosyllabic “lup”
sound. Following a brief delay, the ventricles contract at the same time forcing blood through the semilunar valves into the
aorta and the artery transporting blood to the lungs (via the pulmonary artery). Closing of the semilunar valves produces a
monosyllabic “dup” sound.
Figure 40.12 During (a) cardiac diastole, the heart muscle is relaxed and blood flows into the heart. During (b) atrial
systole, the atria contract, pushing blood into the ventricles. During (c) atrial diastole, the ventricles contract, forcing
blood out of the heart.
The pumping of the heart is a function of the cardiac muscle cells, or cardiomyocytes, that make up the heart muscle.
Cardiomyocytes , shown in Figure 40.13 , are distinctive muscle cells that are striated like skeletal muscle but pump
rhythmically and involuntarily like smooth muscle; they are connected by intercalated disks exclusive to cardiac muscle.
They are self-stimulated for a period of time and isolated cardiomyocytes will beat if given the correct balance of nutrients
and electrolytes.
1176 Chapter 40 | The Circulatory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 40.13 Cardiomyocytes are striated muscle cells found in cardiac tissue. (credit: modification of work by Dr. S.
Girod, Anton Becker; scale-bar data from Matt Russell)
The autonomous beating of cardiac muscle cells is regulated by the heart’s internal pacemaker that uses electrical signals
to time the beating of the heart. The electrical signals and mechanical actions, illustrated in Figure 40.14 , are intimately
intertwined. The internal pacemaker starts at the sinoatrial (SA) node , which is located near the wall of the right atrium.
Electrical charges spontaneously pulse from the SA node causing the two atria to contract in unison. The pulse reaches
a second node, called the atrioventricular (AV) node, between the right atrium and right ventricle where it pauses for
approximately 0.1 second before spreading to the walls of the ventricles. From the AV node, the electrical impulse enters
the bundle of His, then to the left and right bundle branches extending through the interventricular septum. Finally, the
Purkinje fibers conduct the impulse from the apex of the heart up the ventricular myocardium, and then the ventricles
contract. This pause allows the atria to empty completely into the ventricles before the ventricles pump out the blood. The
electrical impulses in the heart produce electrical currents that flow through the body and can be measured on the skin using
electrodes. This information can be observed as an electrocardiogram (ECG) —a recording of the electrical impulses of
the cardiac muscle.
Figure 40.14 The beating of the heart is regulated by an electrical impulse that causes the characteristic reading of an
ECG. The signal is initiated at the sinoatrial valve. The signal then (a) spreads to the atria, causing them to contract.
The signal is (b) delayed at the atrioventricular node before it is passed on to the (c) heart apex. The delay allows the
atria to relax before the (d) ventricles contract. The final part of the ECG cycle prepares the heart for the next beat.
Chapter 40 | The Circulatory System 1177 Visit this site (http://openstaxcollege.org/l/electric_heart) to see the heart’s “pacemaker” in action.
Arteries, Veins, and Capillaries
The blood from the heart is carried through the body by a complex network of blood vessels ( Figure 40.15 ).Arteries take
blood away from the heart. The main artery is the aorta that branches into major arteries that take blood to different limbs
and organs. These major arteries include the carotid artery that takes blood to the brain, the brachial arteries that take blood
to the arms, and the thoracic artery that takes blood to the thorax and then into the hepatic, renal, and gastric arteries for
the liver, kidney, and stomach, respectively. The iliac artery takes blood to the lower limbs. The major arteries diverge into
minor arteries, and then smaller vessels called arterioles , to reach more deeply into the muscles and organs of the body.
Figure 40.15 The major human arteries and veins are shown. (credit: modification of work by Mariana Ruiz Villareal)
Arterioles diverge into capillary beds. Capillary beds contain a large number (10 to 100) of capillaries that branch among
the cells and tissues of the body. Capillaries are narrow-diameter tubes that can fit red blood cells through in single file and
are the sites for the exchange of nutrients, waste, and oxygen with tissues at the cellular level. Fluid also crosses into the
interstitial space from the capillaries. The capillaries converge again into venules that connect to minor veins that finally
connect to major veins that take blood high in carbon dioxide back to the heart. Veins are blood vessels that bring blood
back to the heart. The major veins drain blood from the same organs and limbs that the major arteries supply. Fluid is also
brought back to the heart via the lymphatic system.
1178 Chapter 40 | The Circulatory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 The structure of the different types of blood vessels reflects their function or layers. There are three distinct layers, or tunics,
that form the walls of blood vessels ( Figure 40.16 ). The first tunic is a smooth, inner lining of endothelial cells that are
in contact with the red blood cells. The endothelial tunic is continuous with the endocardium of the heart. In capillaries,
this single layer of cells is the location of diffusion of oxygen and carbon dioxide between the endothelial cells and red
blood cells, as well as the exchange site via endocytosis and exocytosis. The movement of materials at the site of capillaries
is regulated by vasoconstriction , narrowing of the blood vessels, and vasodilation , widening of the blood vessels; this is
important in the overall regulation of blood pressure.
Veins and arteries both have two further tunics that surround the endothelium: the middle tunic is composed of smooth
muscle and the outermost layer is connective tissue (collagen and elastic fibers). The elastic connective tissue stretches
and supports the blood vessels, and the smooth muscle layer helps regulate blood flow by altering vascular resistance
through vasoconstriction and vasodilation. The arteries have thicker smooth muscle and connective tissue than the veins to
accommodate the higher pressure and speed of freshly pumped blood. The veins are thinner walled as the pressure and rate
of flow are much lower. In addition, veins are structurally different than arteries in that veins have valves to prevent the
backflow of blood. Because veins have to work against gravity to get blood back to the heart, contraction of skeletal muscle
assists with the flow of blood back to the heart.
Figure 40.16 Arteries and veins consist of three layers: an outer tunica externa, a middle tunica media, and an inner
tunica intima. Capillaries consist of a single layer of epithelial cells, the tunica intima. (credit: modification of work by
NCI, NIH)
40.4 | Blood Flow and Blood Pressure Regulation
By the end of this section, you will be able to:
• Describe the system of blood flow through the body
• Describe how blood pressure is regulated
Blood pressure (BP) is the pressure exerted by blood on the walls of a blood vessel that helps to push blood through
the body. Systolic blood pressure measures the amount of pressure that blood exerts on vessels while the heart is beating.
The optimal systolic blood pressure is 120 mmHg. Diastolic blood pressure measures the pressure in the vessels between
heartbeats. The optimal diastolic blood pressure is 80 mmHg. Many factors can affect blood pressure, such as hormones,
stress, exercise, eating, sitting, and standing. Blood flow through the body is regulated by the size of blood vessels, by the
action of smooth muscle, by one-way valves, and by the fluid pressure of the blood itself.
How Blood Flows Through the Body
Blood is pushed through the body by the action of the pumping heart. With each rhythmic pump, blood is pushed under
high pressure and velocity away from the heart, initially along the main artery, the aorta. In the aorta, the blood travels at
Chapter 40 | The Circulatory System 1179 30 cm/sec. As blood moves into the arteries, arterioles, and ultimately to the capillary beds, the rate of movement slows
dramatically to about 0.026 cm/sec, one-thousand times slower than the rate of movement in the aorta. While the diameter of
each individual arteriole and capillary is far narrower than the diameter of the aorta, and according to the law of continuity,
fluid should travel faster through a narrower diameter tube, the rate is actually slower due to the overall diameter of all the
combined capillaries being far greater than the diameter of the individual aorta.
The slow rate of travel through the capillary beds, which reach almost every cell in the body, assists with gas and nutrient
exchange and also promotes the diffusion of fluid into the interstitial space. After the blood has passed through the capillary
beds to the venules, veins, and finally to the main venae cavae, the rate of flow increases again but is still much slower than
the initial rate in the aorta. Blood primarily moves in the veins by the rhythmic movement of smooth muscle in the vessel
wall and by the action of the skeletal muscle as the body moves. Because most veins must move blood against the pull of
gravity, blood is prevented from flowing backward in the veins by one-way valves. Because skeletal muscle contraction
aids in venous blood flow, it is important to get up and move frequently after long periods of sitting so that blood will not
pool in the extremities.
Blood flow through the capillary beds is regulated depending on the body’s needs and is directed by nerve and hormone
signals. For example, after a large meal, most of the blood is diverted to the stomach by vasodilation of vessels of the
digestive system and vasoconstriction of other vessels. During exercise, blood is diverted to the skeletal muscles through
vasodilation while blood to the digestive system would be lessened through vasoconstriction. The blood entering some
capillary beds is controlled by small muscles, called precapillary sphincters, illustrated in Figure 40.17 . If the sphincters
are open, the blood will flow into the associated branches of the capillary blood. If all of the sphincters are closed, then the
blood will flow directly from the arteriole to the venule through the thoroughfare channel (see Figure 40.17 ). These muscles
allow the body to precisely control when capillary beds receive blood flow. At any given moment only about 5-10% of our
capillary beds actually have blood flowing through them.
Figure 40.17 (a) Precapillary sphincters are rings of smooth muscle that regulate the flow of blood through
capillaries; they help control the location of blood flow to where it is needed. (b) Valves in the veins prevent blood
from moving backward. (credit a: modification of work by NCI)
Varicose veins are veins that become enlarged because the valves no longer close properly, allowing blood
to flow backward. Varicose veins are often most prominent on the legs. Why do you think this is the case?
Visit this site (http://openstaxcollege.org/l/circulation) to see the circulatory system’s blood flow.
Proteins and other large solutes cannot leave the capillaries. The loss of the watery plasma creates a hyperosmotic solution
within the capillaries, especially near the venules. This causes about 85% of the plasma that leaves the capillaries to
1180 Chapter 40 | The Circulatory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 eventually diffuses back into the capillaries near the venules. The remaining 15% of blood plasma drains out from the
interstitial fluid into nearby lymphatic vessels ( Figure 40.18 ). The fluid in the lymph is similar in composition to the
interstitial fluid. The lymph fluid passes through lymph nodes before it returns to the heart via the vena cava. Lymph nodes
are specialized organs that filter the lymph by percolation through a maze of connective tissue filled with white blood cells.
The white blood cells remove infectious agents, such as bacteria and viruses, to clean the lymph before it returns to the
bloodstream. After it is cleaned, the lymph returns to the heart by the action of smooth muscle pumping, skeletal muscle
action, and one-way valves joining the returning blood near the junction of the venae cavae entering the right atrium of the
heart.
Figure 40.18 Fluid from the capillaries moves into the interstitial space and lymph capillaries by diffusion down a
pressure gradient and also by osmosis. Out of 7,200 liters of fluid pumped by the average heart in a day, over 1,500
liters is filtered. (credit: modification of work by NCI, NIH)
Vertebrate Diversity in Blood Circulation
Blood circulation has evolved differently in vertebrates and may show variation in different animals for the
required amount of pressure, organ and vessel location, and organ size. Animals with longs necks and those
that live in cold environments have distinct blood pressure adaptations.
Long necked animals, such as giraffes, need to pump blood upward from the heart against gravity. The
blood pressure required from the pumping of the left ventricle would be equivalent to 250 mm Hg (mm Hg
= millimeters of mercury, a unit of pressure) to reach the height of a giraffe’s head, which is 2.5 meters
higher than the heart. However, if checks and balances were not in place, this blood pressure would damage
the giraffe’s brain, particularly if it was bending down to drink. These checks and balances include valves
and feedback mechanisms that reduce the rate of cardiac output. Long-necked dinosaurs such as the
sauropods had to pump blood even higher, up to ten meters above the heart. This would have required
a blood pressure of more than 600 mm Hg, which could only have been achieved by an enormous heart.
Evidence for such an enormous heart does not exist and mechanisms to reduce the blood pressure required
include the slowing of metabolism as these animals grew larger. It is likely that they did not routinely feed
on tree tops but grazed on the ground.
Living in cold water, whales need to maintain the temperature in their blood. This is achieved by the
veins and arteries being close together so that heat exchange can occur. This mechanism is called a
countercurrent heat exchanger. The blood vessels and the whole body are also protected by thick layers
of blubber to prevent heat loss. In land animals that live in cold environments, thick fur and hibernation are
used to retain heat and slow metabolism.
Chapter 40 | The Circulatory System 1181 Blood Pressure
The pressure of the blood flow in the body is produced by the hydrostatic pressure of the fluid (blood) against the walls of
the blood vessels. Fluid will move from areas of high to low hydrostatic pressures. In the arteries, the hydrostatic pressure
near the heart is very high and blood flows to the arterioles where the rate of flow is slowed by the narrow openings of the
arterioles. During systole, when new blood is entering the arteries, the artery walls stretch to accommodate the increase of
pressure of the extra blood; during diastole, the walls return to normal because of their elastic properties. The blood pressure
of the systole phase and the diastole phase, graphed in Figure 40.19 , gives the two pressure readings for blood pressure.
For example, 120/80 indicates a reading of 120 mm Hg during the systole and 80 mm Hg during diastole. Throughout the
cardiac cycle, the blood continues to empty into the arterioles at a relatively even rate. This resistance to blood flow is called
peripheral resistance .
Figure 40.19 Blood pressure is related to the blood velocity in the arteries and arterioles. In the capillaries and veins,
the blood pressure continues to decease but velocity increases.
Blood Pressure Regulation
Cardiac output is the volume of blood pumped by the heart in one minute. It is calculated by multiplying the number of
heart contractions that occur per minute (heart rate) times the stroke volume (the volume of blood pumped into the aorta
per contraction of the left ventricle). Therefore, cardiac output can be increased by increasing heart rate, as when exercising.
However, cardiac output can also be increased by increasing stroke volume, such as if the heart contracts with greater
strength. Stroke volume can also be increased by speeding blood circulation through the body so that more blood enters the
heart between contractions. During heavy exertion, the blood vessels relax and increase in diameter, offsetting the increased
heart rate and ensuring adequate oxygenated blood gets to the muscles. Stress triggers a decrease in the diameter of the
blood vessels, consequently increasing blood pressure. These changes can also be caused by nerve signals or hormones, and
even standing up or lying down can have a great effect on blood pressure.
1182 Chapter 40 | The Circulatory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 angina
aorta
arteriole
artery
atherosclerosis
atrioventricular valve
atrium
bicuspid valve
blood pressure (BP)
capillary
capillary bed
cardiac cycle
cardiac output
cardiomyocyte
closed circulatory system
coronary artery
coronary vein
diastole
double circulation
electrocardiogram (ECG)
endocardium
epicardium
gill circulation
hemocoel
hemolymph
inferior vena cava
KEY TERMS
pain caused by partial blockage of the coronary arteries by the buildup of plaque and lack of oxygen to the heart
muscle
major artery of the body that takes blood away from the heart
small vessel that connects an artery to a capillary bed
blood vessel that takes blood away from the heart
buildup of fatty plaques in the coronary arteries in the heart
one-way membranous flap of connective tissue between the atrium and the ventricle in the right
side of the heart; also known as tricuspid valve
(plural: atria) chamber of the heart that receives blood from the veins and sends blood to the ventricles
(also, mitral valve; left atrioventricular valve) one-way membranous flap between the atrium and the
ventricle in the left side of the heart
pressure of blood in the arteries that helps to push blood through the body
smallest blood vessel that allows the passage of individual blood cells and the site of diffusion of oxygen and
nutrient exchange
large number of capillaries that converge to take blood to a particular organ or tissue
filling and emptying the heart of blood by electrical signals that cause the heart muscles to contract and
relax
the volume of blood pumped by the heart in one minute as a product of heart rate multiplied by stroke
volume
specialized heart muscle cell that is striated but contracts involuntarily like smooth muscle
system in which the blood is separated from the bodily interstitial fluid and contained in
blood vessels
vessel that supplies the heart tissue with blood
vessel that takes blood away from the heart tissue back to the chambers in the heart
relaxation phase of the cardiac cycle when the heart is relaxed and the ventricles are filling with blood
flow of blood in two circuits: the pulmonary circuit through the lungs and the systemic circuit
through the organs and body
recording of the electrical impulses of the cardiac muscle
innermost layer of tissue in the heart
outermost tissue layer of the heart
circulatory system that is specific to animals with gills for gas exchange; the blood flows through the gills
for oxygenation
cavity into which blood is pumped in an open circulatory system
mixture of blood and interstitial fluid that is found in insects and other arthropods as well as most mollusks
drains blood from the veins that come from the lower organs and the legs
Chapter 40 | The Circulatory System 1183 interstitial fluid
lymph node
myocardial infarction
myocardium
open circulatory system
ostium
pericardium
peripheral resistance
plasma
platelet
precapillary sphincter
pulmocutaneous circulation
pulmonary circulation
red blood cell
semilunar valve
serum
sinoatrial (SA) node
stroke volume>
superior vena cava
systemic circulation
systole
tricuspid valve
unidirectional circulation
vasoconstriction
vasodilation
fluid between cells
specialized organ that contains a large number of macrophages that clean the lymph before the fluid is
returned to the heart
(also, heart attack) complete blockage of the coronary arteries and death of the cardiac muscle
tissue
heart muscle cells that make up the middle layer and the bulk of the heart wall
system in which the blood is mixed with interstitial fluid and directly covers the organs
(plural: ostia) holes between blood vessels that allow the movement of hemolymph through the body of insects,
arthropods, and mollusks with open circulatory systems
membrane layer protecting the heart; also part of the epicardium
resistance of the artery and blood vessel walls to the pressure placed on them by the force of the
heart pumping
liquid component of blood that is left after the cells are removed
(also, thrombocyte) small cellular fragment that collects at wounds, cross-reacts with clotting factors, and forms a
plug to prevent blood loss
small muscle that controls blood circulation in the capillary beds
circulatory system in amphibians; the flow of blood to the lungs and the moist skin for
gas exchange
flow of blood away from the heart through the lungs where oxygenation occurs and then returns
to the heart again
small (7–8 μm) biconcave cell without mitochondria (and in mammals without nuclei) that is packed with
hemoglobin, giving the cell its red color; transports oxygen through the body
membranous flap of connective tissue between the aorta and a ventricle of the heart (the aortic or
pulmonary semilunar valves)
plasma without the coagulation factors
the heart’s internal pacemaker; located near the wall of the right atrium
- the volume of blood pumped into the aorta per contraction of the left ventricle
drains blood from the jugular vein that comes from the brain and from the veins that come from the
arms
flow of blood away from the heart to the brain, liver, kidneys, stomach, and other organs, the limbs,
and the muscles of the body, and then the return of this blood to the heart
contraction phase of cardiac cycle when the ventricles are pumping blood into the arteries
one-way membranous flap of connective tissue between the atrium and the ventricle in the right side of
the heart; also known as atrioventricular valve
flow of blood in a single circuit; occurs in fish where the blood flows through the gills, then
past the organs and the rest of the body, before returning to the heart
narrowing of a blood vessel
widening of a blood vessel
1184 Chapter 40 | The Circulatory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 vein
vena cava
ventricle
venule
white blood cell
blood vessel that brings blood back to the heart
major vein of the body returning blood from the upper and lower parts of the body; see the superior vena cava
and inferior vena cava
(heart) large inferior chamber of the heart that pumps blood into arteries
blood vessel that connects a capillary bed to a vein
large (30 μm) cell with nuclei of which there are many types with different roles including the protection
of the body from viruses and bacteria, and cleaning up dead cells and other waste
CHAPTER SUMMARY
40.1 Overview of the Circulatory System
In most animals, the circulatory system is used to transport blood through the body. Some primitive animals use diffusion
for the exchange of water, nutrients, and gases. However, complex organisms use the circulatory system to carry gases,
nutrients, and waste through the body. Circulatory systems may be open (mixed with the interstitial fluid) or closed
(separated from the interstitial fluid). Closed circulatory systems are a characteristic of vertebrates; however, there are
significant differences in the structure of the heart and the circulation of blood between the different vertebrate groups due
to adaptions during evolution and associated differences in anatomy. Fish have a two-chambered heart with unidirectional
circulation. Amphibians have a three-chambered heart, which has some mixing of the blood, and they have double
circulation. Most non-avian reptiles have a three-chambered heart, but have little mixing of the blood; they have double
circulation. Mammals and birds have a four-chambered heart with no mixing of the blood and double circulation.
40.2 Components of the Blood
Specific components of the blood include red blood cells, white blood cells, platelets, and the plasma, which contains
coagulation factors and serum. Blood is important for regulation of the body’s pH, temperature, osmotic pressure, the
circulation of nutrients and removal of waste, the distribution of hormones from endocrine glands, and the elimination of
excess heat; it also contains components for blood clotting. Red blood cells are specialized cells that contain hemoglobin
and circulate through the body delivering oxygen to cells. White blood cells are involved in the immune response to
identify and target invading bacteria, viruses, and other foreign organisms; they also recycle waste components, such as
old red blood cells. Platelets and blood clotting factors cause the change of the soluble protein fibrinogen to the insoluble
protein fibrin at a wound site forming a plug. Plasma consists of 90 percent water along with various substances, such as
coagulation factors and antibodies. The serum is the plasma component of the blood without the coagulation factors.
40.3 Mammalian Heart and Blood Vessels
The heart muscle pumps blood through three divisions of the circulatory system: coronary, pulmonary, and systemic.
There is one atrium and one ventricle on the right side and one atrium and one ventricle on the left side. The pumping of
the heart is a function of cardiomyocytes, distinctive muscle cells that are striated like skeletal muscle but pump
rhythmically and involuntarily like smooth muscle. The internal pacemaker starts at the sinoatrial node, which is located
near the wall of the right atrium. Electrical charges pulse from the SA node causing the two atria to contract in unison;
then the pulse reaches the atrioventricular node between the right atrium and right ventricle. A pause in the electric signal
allows the atria to empty completely into the ventricles before the ventricles pump out the blood. The blood from the heart
is carried through the body by a complex network of blood vessels; arteries take blood away from the heart, and veins
bring blood back to the heart.
40.4 Blood Flow and Blood Pressure Regulation
Blood primarily moves through the body by the rhythmic movement of smooth muscle in the vessel wall and by the action
of the skeletal muscle as the body moves. Blood is prevented from flowing backward in the veins by one-way valves.
Blood flow through the capillary beds is controlled by precapillary sphincters to increase and decrease flow depending on
the body’s needs and is directed by nerve and hormone signals. Lymph vessels take fluid that has leaked out of the blood
to the lymph nodes where it is cleaned before returning to the heart. During systole, blood enters the arteries, and the artery
walls stretch to accommodate the extra blood. During diastole, the artery walls return to normal. The blood pressure of the
systole phase and the diastole phase gives the two pressure readings for blood pressure.
Chapter 40 | The Circulatory System 1185 ART CONNECTION QUESTIONS
1. Figure 40.10 Which of the following statements about
the circulatory system is false?
a. Blood in the pulmonary vein is deoxygenated.
b. Blood in the inferior vena cava is deoxygenated.
c. Blood in the pulmonary artery is deoxygenated.
d. Blood in the aorta is oxygenated.
2. Figure 40.11 Which of the following statements about
the heart is false?
a. The mitral valve separates the left ventricle from
the left atrium.
b. Blood travels through the bicuspid valve to the
left atrium.
c. Both the aortic and the pulmonary valves are
semilunar valves.
d. The mitral valve is an atrioventricular valve.
3. Figure 40.17 Varicose veins are veins that become
enlarged because the valves no longer close properly,
allowing blood to flow backward. Varicose veins are often
most prominent on the legs. Why do you think this is the
case?
REVIEW QUESTIONS
4. Why are open circulatory systems advantageous to
some animals?
a. They use less metabolic energy.
b. They help the animal move faster.
c. They do not need a heart.
d. They help large insects develop.
5. Some animals use diffusion instead of a circulatory
system. Examples include:
a. birds and jellyfish
b. flatworms and arthropods
c. mollusks and jellyfish
d. None of the above
6. Blood flow that is directed through the lungs and back
to the heart is called ________.
a. unidirectional circulation
b. gill circulation
c. pulmonary circulation
d. pulmocutaneous circulation
7. White blood cells:
a. can be classified as granulocytes or
agranulocytes
b. defend the body against bacteria and viruses
c. are also called leucocytes
d. All of the above
8. Platelet plug formation occurs at which point?
a. when large megakaryocytes break up into
thousands of smaller fragments
b. when platelets are dispersed through the blood
stream
c. when platelets are attracted to a site of blood
vessel damage
d. none of the above
9. In humans, the plasma comprises what percentage of
the blood?
a. 45 percent
b. 55 percent
c. 25 percent
d. 90 percent
10. The red blood cells of birds differ from mammalian
red blood cells because:
a. they are white and have nuclei
b. they do not have nuclei
c. they have nuclei
d. they fight disease
11. The heart’s internal pacemaker beats by:
a. an internal implant that sends an electrical
impulse through the heart
b. the excitation of cardiac muscle cells at the
sinoatrial node followed by the atrioventricular
node
c. the excitation of cardiac muscle cells at the
atrioventricular node followed by the sinoatrial
node
d. the action of the sinus
12. During the systolic phase of the cardiac cycle, the
heart is ________.
a. contracting
b. relaxing
c. contracting and relaxing
d. filling with blood
13. Cardiomyocytes are similar to skeletal muscle
because:
a. they beat involuntarily
b. they are used for weight lifting
c. they pulse rhythmically
d. they are striated
14. How do arteries differ from veins?
a. Arteries have thicker smooth muscle layers to
accommodate the changes in pressure from the
heart.
b. Arteries carry blood.
c. Arteries have thinner smooth muscle layers and
valves and move blood by the action of skeletal
muscle.
d. Arteries are thin walled and are used for gas
exchange.
15. High blood pressure would be a result of ________.
1186 Chapter 40 | The Circulatory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 a. a high cardiac output and high peripheral
resistance
b. a high cardiac output and low peripheral
resistance
c. a low cardiac output and high peripheral
resistance
d. a low cardiac output and low peripheral
resistance
CRITICAL THINKING QUESTIONS
16. Describe a closed circulatory system.
17. Describe systemic circulation.
18. Describe the cause of different blood type groups.
19. List some of the functions of blood in the body.
20. How does the lymphatic system work with blood
flow?
21. Describe the cardiac cycle.
22. What happens in capillaries?
23. How does blood pressure change during heavy
exercise?
Chapter 40 | The Circulatory System 1187 1188 Chapter 40 | The Circulatory System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 41 | OSMOTIC
REGULATION AND
EXCRETION
Figure 41.1 Just as humans recycle what we can and dump the remains into landfills, our bodies use and recycle what
they can and excrete the remaining waste products. Our bodies’ complex systems have developed ways to treat waste
and maintain a balanced internal environment. (credit: modification of work by Redwin Law)
Chapter Outline
41.1: Osmoregulation and Osmotic Balance
41.2: The Kidneys and Osmoregulatory Organs
41.3: Excretion Systems
41.4: Nitrogenous Wastes
41.5: Hormonal Control of Osmoregulatory Functions
Introduction
The daily intake recommendation for human water consumption is eight to ten glasses of water. In order to achieve a
healthy balance, the human body should excrete the eight to ten glasses of water every day. This occurs via the processes
of urination, defecation, sweating and, to a small extent, respiration. The organs and tissues of the human body are soaked
in fluids that are maintained at constant temperature, pH, and solute concentration, all crucial elements of homeostasis. The
solutes in body fluids are mainly mineral salts and sugars, and osmotic regulation is the process by which the mineral salts
and water are kept in balance. Osmotic homeostasis is maintained despite the influence of external factors like temperature,
diet, and weather conditions.
Chapter 41 | Osmotic Regulation and Excretion 1189 41.1 | Osmoregulation and Osmotic Balance
By the end of this section, you will be able to:
• Define osmosis and explain its role within molecules
• Explain why osmoregulation and osmotic balance are important body functions
• Describe active transport mechanisms
• Explain osmolarity and the way in which it is measured
• Describe osmoregulators or osmoconformers and how these tools allow animals to adapt to different environments
Osmosis is the diffusion of water across a membrane in response to osmotic pressure caused by an imbalance of molecules
on either side of the membrane. Osmoregulation is the process of maintenance of salt and water balance ( osmotic balance )
across membranes within the body’s fluids, which are composed of water, plus electrolytes and non-electrolytes. An
electrolyte is a solute that dissociates into ions when dissolved in water. A non-electrolyte , in contrast, doesn’t dissociate
into ions during water dissolution. Both electrolytes and non-electrolytes contribute to the osmotic balance. The body’s
fluids include blood plasma, the cytosol within cells, and interstitial fluid, the fluid that exists in the spaces between cells
and tissues of the body. The membranes of the body (such as the pleural, serous, and cell membranes) are semi-permeable
membranes . Semi-permeable membranes are permeable (or permissive) to certain types of solutes and water. Solutions
on two sides of a semi-permeable membrane tend to equalize in solute concentration by movement of solutes and/or water
across the membrane. As seen in Figure 41.2 , a cell placed in water tends to swell due to gain of water from the hypotonic
or “low salt” environment. A cell placed in a solution with higher salt concentration, on the other hand, tends to make
the membrane shrivel up due to loss of water into the hypertonic or “high salt” environment. Isotonic cells have an equal
concentration of solutes inside and outside the cell; this equalizes the osmotic pressure on either side of the cell membrane
which is a semi-permeable membrane.
Figure 41.2 Cells placed in a hypertonic environment tend to shrink due to loss of water. In a hypotonic environment,
cells tend to swell due to intake of water. The blood maintains an isotonic environment so that cells neither shrink nor
swell. (credit: Mariana Ruiz Villareal)
The body does not exist in isolation. There is a constant input of water and electrolytes into the system. While
osmoregulation is achieved across membranes within the body, excess electrolytes and wastes are transported to the kidneys
and excreted, helping to maintain osmotic balance.
Need for Osmoregulation
Biological systems constantly interact and exchange water and nutrients with the environment by way of consumption of
food and water and through excretion in the form of sweat, urine, and feces. Without a mechanism to regulate osmotic
pressure, or when a disease damages this mechanism, there is a tendency to accumulate toxic waste and water, which can
have dire consequences.
Mammalian systems have evolved to regulate not only the overall osmotic pressure across membranes, but also specific
concentrations of important electrolytes in the three major fluid compartments: blood plasma, extracellular fluid, and
1190 Chapter 41 | Osmotic Regulation and Excretion
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 intracellular fluid. Since osmotic pressure is regulated by the movement of water across membranes, the volume of the fluid
compartments can also change temporarily. Because blood plasma is one of the fluid components, osmotic pressures have a
direct bearing on blood pressure.
Transport of Electrolytes across Cell Membranes
Electrolytes, such as sodium chloride, ionize in water, meaning that they dissociate into their component ions. In water,
sodium chloride (NaCl), dissociates into the sodium ion (Na +) and the chloride ion (Cl –). The most important ions,
whose concentrations are very closely regulated in body fluids, are the cations sodium (Na +), potassium (K +), calcium
(Ca +2), magnesium (Mg +2), and the anions chloride (Cl -), carbonate (CO 3-2), bicarbonate (HCO 3-), and phosphate(PO 3-).
Electrolytes are lost from the body during urination and perspiration. For this reason, athletes are encouraged to replace
electrolytes and fluids during periods of increased activity and perspiration.
Osmotic pressure is influenced by the concentration of solutes in a solution. It is directly proportional to the number of
solute atoms or molecules and not dependent on the size of the solute molecules. Because electrolytes dissociate into their
component ions, they, in essence, add more solute particles into the solution and have a greater effect on osmotic pressure,
per mass than compounds that do not dissociate in water, such as glucose.
Water can pass through membranes by passive diffusion. If electrolyte ions could passively diffuse across membranes, it
would be impossible to maintain specific concentrations of ions in each fluid compartment therefore they require special
mechanisms to cross the semi-permeable membranes in the body. This movement can be accomplished by facilitated
diffusion and active transport. Facilitated diffusion requires protein-based channels for moving the solute. Active transport
requires energy in the form of ATP conversion, carrier proteins, or pumps in order to move ions against the concentration
gradient.
Concept of Osmolality and Milliequivalent
In order to calculate osmotic pressure, it is necessary to understand how solute concentrations are measured. The unit for
measuring solutes is the mole . One mole is defined as the gram molecular weight of the solute. For example, the molecular
weight of sodium chloride is 58.44. Thus, one mole of sodium chloride weighs 58.44 grams. The molarity of a solution is
the number of moles of solute per liter of solution. The molality of a solution is the number of moles of solute per kilogram
of solvent. If the solvent is water, one kilogram of water is equal to one liter of water. While molarity and molality are used
to express the concentration of solutions, electrolyte concentrations are usually expressed in terms of milliequivalents per
liter (mEq/L): the mEq/L is equal to the ion concentration (in millimoles) multiplied by the number of electrical charges on
the ion. The unit of milliequivalent takes into consideration the ions present in the solution (since electrolytes form ions in
aqueous solutions) and the charge on the ions.
Thus, for ions that have a charge of one, one milliequivalent is equal to one millimole. For ions that have a charge of two
(like calcium), one milliequivalent is equal to 0.5 millimoles. Another unit for the expression of electrolyte concentration is
the milliosmole (mOsm), which is the number of milliequivalents of solute per kilogram of solvent. Body fluids are usually
maintained within the range of 280 to 300 mOsm.
Osmoregulators and Osmoconformers
Persons lost at sea without any fresh water to drink are at risk of severe dehydration because the human body cannot adapt
to drinking seawater, which is hypertonic in comparison to body fluids. Organisms such as goldfish that can tolerate only
a relatively narrow range of salinity are referred to as stenohaline. About 90 percent of all bony fish are restricted to either
freshwater or seawater. They are incapable of osmotic regulation in the opposite environment. It is possible, however, for
a few fishes like salmon to spend part of their life in fresh water and part in sea water. Organisms like the salmon and
molly that can tolerate a relatively wide range of salinity are referred to as euryhaline organisms. This is possible because
some fish have evolved osmoregulatory mechanisms to survive in all kinds of aquatic environments. When they live in
fresh water, their bodies tend to take up water because the environment is relatively hypotonic, as illustrated in Figure
41.3 a. In such hypotonic environments, these fish do not drink much water. Instead, they pass a lot of very dilute urine,
and they achieve electrolyte balance by active transport of salts through the gills. When they move to a hypertonic marine
environment, these fish start drinking sea water; they excrete the excess salts through their gills and their urine, as illustrated
in Figure 41.3 b. Most marine invertebrates, on the other hand, may be isotonic with sea water ( osmoconformers ). Their
body fluid concentrations conform to changes in seawater concentration. Cartilaginous fishes’ salt composition of the blood
is similar to bony fishes; however, the blood of sharks contains the organic compounds urea and trimethylamine oxide
(TMAO). This does not mean that their electrolyte composition is similar to that of sea water. They achieve isotonicity
with the sea by storing large concentrations of urea. These animals that secrete urea are called ureotelic animals. TMAO
stabilizes proteins in the presence of high urea levels, preventing the disruption of peptide bonds that would occur in other
Chapter 41 | Osmotic Regulation and Excretion 1191 animals exposed to similar levels of urea. Sharks are cartilaginous fish with a rectal gland to secrete salt and assist in
osmoregulation.
Figure 41.3 Fish are osmoregulators, but must use different mechanisms to survive in (a) freshwater or (b) saltwater
environments. (credit: modification of work by Duane Raver, NOAA)
Dialysis Technician
Dialysis is a medical process of removing wastes and excess water from the blood by diffusion and
ultrafiltration. When kidney function fails, dialysis must be done to artificially rid the body of wastes. This is
a vital process to keep patients alive. In some cases, the patients undergo artificial dialysis until they are
eligible for a kidney transplant. In others who are not candidates for kidney transplants, dialysis is a life-long
necessity.
Dialysis technicians typically work in hospitals and clinics. While some roles in this field include equipment
development and maintenance, most dialysis technicians work in direct patient care. Their on-the-job
duties, which typically occur under the direct supervision of a registered nurse, focus on providing dialysis
treatments. This can include reviewing patient history and current condition, assessing and responding to
patient needs before and during treatment, and monitoring the dialysis process. Treatment may include
taking and reporting a patient’s vital signs and preparing solutions and equipment to ensure accurate and
sterile procedures.
1192 Chapter 41 | Osmotic Regulation and Excretion
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 41.2 | The Kidneys and Osmoregulatory Organs
By the end of this section, you will be able to:
• Explain how the kidneys serve as the main osmoregulatory organs in mammalian systems
• Describe the structure of the kidneys and the functions of the parts of the kidney
• Describe how the nephron is the functional unit of the kidney and explain how it actively filters blood and generates
urine
• Detail the three steps in the formation of urine: glomerular filtration, tubular reabsorption, and tubular secretion
Although the kidneys are the major osmoregulatory organ, the skin and lungs also play a role in the process. Water and
electrolytes are lost through sweat glands in the skin, which helps moisturize and cool the skin surface, while the lungs
expel a small amount of water in the form of mucous secretions and via evaporation of water vapor.
Kidneys: The Main Osmoregulatory Organ
The kidneys , illustrated in Figure 41.4 , are a pair of bean-shaped structures that are located just below and posterior to the
liver in the peritoneal cavity. The adrenal glands sit on top of each kidney and are also called the suprarenal glands. Kidneys
filter blood and purify it. All the blood in the human body is filtered many times a day by the kidneys; these organs use
up almost 25 percent of the oxygen absorbed through the lungs to perform this function. Oxygen allows the kidney cells
to efficiently manufacture chemical energy in the form of ATP through aerobic respiration. The filtrate coming out of the
kidneys is called urine .
Figure 41.4 Kidneys filter the blood, producing urine that is stored in the bladder prior to elimination through the
urethra. (credit: modification of work by NCI)
Kidney Structure
Externally, the kidneys are surrounded by three layers, illustrated in Figure 41.5 . The outermost layer is a tough connective
tissue layer called the renal fascia . The second layer is called the perirenal fat capsule , which helps anchor the kidneys
in place. The third and innermost layer is the renal capsule . Internally, the kidney has three regions—an outer cortex ,a
medulla in the middle, and the renal pelvis in the region called the hilum of the kidney. The hilum is the concave part of
the bean-shape where blood vessels and nerves enter and exit the kidney; it is also the point of exit for the ureters. The renal
cortex is granular due to the presence of nephrons —the functional unit of the kidney. The medulla consists of multiple
pyramidal tissue masses, called the renal pyramids . In between the pyramids are spaces called renal columns through
Chapter 41 | Osmotic Regulation and Excretion 1193 which the blood vessels pass. The tips of the pyramids, called renal papillae, point toward the renal pelvis. There are, on
average, eight renal pyramids in each kidney. The renal pyramids along with the adjoining cortical region are called the
lobes of the kidney . The renal pelvis leads to the ureter on the outside of the kidney. On the inside of the kidney, the renal
pelvis branches out into two or three extensions called the major calyces , which further branch into the minor calyces. The
ureters are urine-bearing tubes that exit the kidney and empty into the urinary bladder .
Figure 41.5 The internal structure of the kidney is shown. (credit: modification of work by NCI)
Which of the following statements about the kidney is false?
a. The renal pelvis drains into the ureter.
b. The renal pyramids are in the medulla.
c. The cortex covers the capsule.
d. Nephrons are in the renal cortex.
Because the kidney filters blood, its network of blood vessels is an important component of its structure and function.
The arteries, veins, and nerves that supply the kidney enter and exit at the renal hilum. Renal blood supply starts with the
branching of the aorta into the renal arteries (which are each named based on the region of the kidney they pass through)
and ends with the exiting of the renal veins to join the inferior vena cava . The renal arteries split into several segmental
arteries upon entering the kidneys. Each segmental artery splits further into several interlobar arteries and enters the renal
columns, which supply the renal lobes. The interlobar arteries split at the junction of the renal cortex and medulla to form the
arcuate arteries . The arcuate “bow shaped” arteries form arcs along the base of the medullary pyramids. Cortical radiate
arteries , as the name suggests, radiate out from the arcuate arteries. The cortical radiate arteries branch into numerous
afferent arterioles, and then enter the capillaries supplying the nephrons. Veins trace the path of the arteries and have similar
names, except there are no segmental veins.
As mentioned previously, the functional unit of the kidney is the nephron, illustrated in Figure 41.6 . Each kidney is made up
of over one million nephrons that dot the renal cortex, giving it a granular appearance when sectioned sagittally. There are
two types of nephrons— cortical nephrons (85 percent), which are deep in the renal cortex, and juxtamedullary nephrons
(15 percent), which lie in the renal cortex close to the renal medulla. A nephron consists of three parts—a renal corpuscle ,
arenal tubule , and the associated capillary network, which originates from the cortical radiate arteries.
1194 Chapter 41 | Osmotic Regulation and Excretion
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 41.6 The nephron is the functional unit of the kidney. The glomerulus and convoluted tubules are located
in the kidney cortex, while collecting ducts are located in the pyramids of the medulla. (credit: modification of work
by NIDDK)
Which of the following statements about the nephron is false?
a. The collecting duct empties into the distal convoluted tubule.
b. The Bowman’s capsule surrounds the glomerulus.
c. The loop of Henle is between the proximal and distal convoluted tubules.
d. The loop of Henle empties into the distal convoluted tubule.
Renal Corpuscle
The renal corpuscle, located in the renal cortex, is made up of a network of capillaries known as the glomerulus and the
capsule, a cup-shaped chamber that surrounds it, called the glomerular or Bowman's capsule .
Renal Tubule
The renal tubule is a long and convoluted structure that emerges from the glomerulus and can be divided into three parts
based on function. The first part is called the proximal convoluted tubule (PCT) due to its proximity to the glomerulus;
it stays in the renal cortex. The second part is called the loop of Henle , or nephritic loop, because it forms a loop (with
descending and ascending limbs ) that goes through the renal medulla. The third part of the renal tubule is called the distal
convoluted tubule (DCT) and this part is also restricted to the renal cortex. The DCT, which is the last part of the nephron,
connects and empties its contents into collecting ducts that line the medullary pyramids. The collecting ducts amass contents
from multiple nephrons and fuse together as they enter the papillae of the renal medulla.
Capillary Network within the Nephron
The capillary network that originates from the renal arteries supplies the nephron with blood that needs to be filtered. The
branch that enters the glomerulus is called the afferent arteriole . The branch that exits the glomerulus is called the efferent
arteriole . Within the glomerulus, the network of capillaries is called the glomerular capillary bed. Once the efferent arteriole
exits the glomerulus, it forms the peritubular capillary network , which surrounds and interacts with parts of the renal
tubule. In cortical nephrons, the peritubular capillary network surrounds the PCT and DCT. In juxtamedullary nephrons, the
peritubular capillary network forms a network around the loop of Henle and is called the vasa recta .
Chapter 41 | Osmotic Regulation and Excretion 1195 Go to this website (http://openstaxcollege.org/l/kidney_section) to see another coronal section of the kidney and to
explore an animation of the workings of nephrons.
Kidney Function and Physiology
Kidneys filter blood in a three-step process. First, the nephrons filter blood that runs through the capillary network in the
glomerulus. Almost all solutes, except for proteins, are filtered out into the glomerulus by a process called glomerular
filtration . Second, the filtrate is collected in the renal tubules. Most of the solutes get reabsorbed in the PCT by a process
called tubular reabsorption . In the loop of Henle, the filtrate continues to exchange solutes and water with the renal
medulla and the peritubular capillary network. Water is also reabsorbed during this step. Then, additional solutes and
wastes are secreted into the kidney tubules during tubular secretion , which is, in essence, the opposite process to tubular
reabsorption. The collecting ducts collect filtrate coming from the nephrons and fuse in the medullary papillae. From here,
the papillae deliver the filtrate, now called urine, into the minor calyces that eventually connect to the ureters through the
renal pelvis. This entire process is illustrated in Figure 41.7 .
1196 Chapter 41 | Osmotic Regulation and Excretion
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 41.7 Each part of the nephron performs a different function in filtering waste and maintaining homeostatic
balance. (1) The glomerulus forces small solutes out of the blood by pressure. (2) The proximal convoluted tubule
reabsorbs ions, water, and nutrients from the filtrate into the interstitial fluid, and actively transports toxins and drugs
from the interstitial fluid into the filtrate. The proximal convoluted tubule also adjusts blood pH by selectively secreting
ammonia (NH 3) into the filtrate, where it reacts with H +to form NH 4+. The more acidic the filtrate, the more ammonia
is secreted. (3) The descending loop of Henle is lined with cells containing aquaporins that allow water to pass from
the filtrate into the interstitial fluid. (4) In the thin part of the ascending loop of Henle, Na +and Cl -ions diffuse into the
interstitial fluid. In the thick part, these same ions are actively transported into the interstitial fluid. Because salt but not
water is lost, the filtrate becomes more dilute as it travels up the limb. (5) In the distal convoluted tubule, K +and H +ions
are selectively secreted into the filtrate, while Na +, Cl -, and HCO 3-ions are reabsorbed to maintain pH and electrolyte
balance in the blood. (6) The collecting duct reabsorbs solutes and water from the filtrate, forming dilute urine. (credit:
modification of work by NIDDK)
Glomerular Filtration
Glomerular filtration filters out most of the solutes due to high blood pressure and specialized membranes in the afferent
arteriole. The blood pressure in the glomerulus is maintained independent of factors that affect systemic blood pressure.
The “leaky” connections between the endothelial cells of the glomerular capillary network allow solutes to pass through
easily. All solutes in the glomerular capillaries, except for macromolecules like proteins, pass through by passive diffusion.
There is no energy requirement at this stage of the filtration process. Glomerular filtration rate (GFR) is the volume
of glomerular filtrate formed per minute by the kidneys. GFR is regulated by multiple mechanisms and is an important
indicator of kidney function.
To learn more about the vascular system of kidneys, click through this review (http://openstaxcollege.org/l/kidneys)
and the steps of blood flow.
Chapter 41 | Osmotic Regulation and Excretion 1197 Tubular Reabsorption and Secretion
Tubular reabsorption occurs in the PCT part of the renal tubule. Almost all nutrients are reabsorbed, and this occurs either
by passive or active transport. Reabsorption of water and some key electrolytes are regulated and can be influenced by
hormones. Sodium (Na +) is the most abundant ion and most of it is reabsorbed by active transport and then transported to
the peritubular capillaries. Because Na +is actively transported out of the tubule, water follows it to even out the osmotic
pressure. Water is also independently reabsorbed into the peritubular capillaries due to the presence of aquaporins, or water
channels, in the PCT. This occurs due to the low blood pressure and high osmotic pressure in the peritubular capillaries.
However, every solute has a transport maximum and the excess is not reabsorbed.
In the loop of Henle, the permeability of the membrane changes. The descending limb is permeable to water, not solutes;
the opposite is true for the ascending limb. Additionally, the loop of Henle invades the renal medulla, which is naturally
high in salt concentration and tends to absorb water from the renal tubule and concentrate the filtrate. The osmotic gradient
increases as it moves deeper into the medulla. Because two sides of the loop of Henle perform opposing functions, as
illustrated in Figure 41.8 ,itactsasa countercurrent multiplier . The vasa recta around it acts as the countercurrent
exchanger .
Figure 41.8 The loop of Henle acts as a countercurrent multiplier that uses energy to create concentration
gradients. The descending limb is water permeable. Water flows from the filtrate to the interstitial fluid, so
osmolality inside the limb increases as it descends into the renal medulla. At the bottom, the osmolality is higher
inside the loop than in the interstitial fluid. Thus, as filtrate enters the ascending limb, Na +and Cl -ions exit through
ion channels present in the cell membrane. Further up, Na +is actively transported out of the filtrate and Cl -follows.
Osmolarity is given in units of milliosmoles per liter (mOsm/L).
Loop diuretics are drugs sometimes used to treat hypertension. These drugs inhibit the reabsorption of Na +
and Cl -ions by the ascending limb of the loop of Henle. A side effect is that they increase urination. Why do
you think this is the case?
By the time the filtrate reaches the DCT, most of the urine and solutes have been reabsorbed. If the body requires additional
water, all of it can be reabsorbed at this point. Further reabsorption is controlled by hormones, which will be discussed in a
later section. Excretion of wastes occurs due to lack of reabsorption combined with tubular secretion. Undesirable products
like metabolic wastes, urea, uric acid, and certain drugs, are excreted by tubular secretion. Most of the tubular secretion
happens in the DCT, but some occurs in the early part of the collecting duct. Kidneys also maintain an acid-base balance by
secreting excess H +ions.
1198 Chapter 41 | Osmotic Regulation and Excretion
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Although parts of the renal tubules are named proximal and distal, in a cross-section of the kidney, the tubules are placed
close together and in contact with each other and the glomerulus. This allows for exchange of chemical messengers between
the different cell types. For example, the DCT ascending limb of the loop of Henle has masses of cells called macula densa ,
which are in contact with cells of the afferent arterioles called juxtaglomerular cells . Together, the macula densa and
juxtaglomerular cells form the juxtaglomerular complex (JGC). The JGC is an endocrine structure that secretes the enzyme
renin and the hormone erythropoietin. When hormones trigger the macula densa cells in the DCT due to variations in blood
volume, blood pressure, or electrolyte balance, these cells can immediately communicate the problem to the capillaries in
the afferent and efferent arterioles, which can constrict or relax to change the glomerular filtration rate of the kidneys.
Nephrologist
A nephrologist studies and deals with diseases of the kidneys—both those that cause kidney failure (such as
diabetes) and the conditions that are produced by kidney disease (such as hypertension). Blood pressure,
blood volume, and changes in electrolyte balance come under the purview of a nephrologist.
Nephrologists usually work with other physicians who refer patients to them or consult with them about
specific diagnoses and treatment plans. Patients are usually referred to a nephrologist for symptoms such
as blood or protein in the urine, very high blood pressure, kidney stones, or renal failure.
Nephrology is a subspecialty of internal medicine. To become a nephrologist, medical school is followed
by additional training to become certified in internal medicine. An additional two or more years is spent
specifically studying kidney disorders and their accompanying effects on the body.
41.3 | Excretion Systems
By the end of this section, you will be able to:
• Explain how vacuoles, present in microorganisms, work to excrete waste
• Describe the way in which flame cells and nephridia in worms perform excretory functions and maintain osmotic
balance
• Explain how insects use Malpighian tubules to excrete wastes and maintain osmotic balance
Microorganisms and invertebrate animals use more primitive and simple mechanisms to get rid of their metabolic wastes
than the mammalian system of kidney and urinary function. Three excretory systems evolved in organisms before complex
kidneys: vacuoles, flame cells, and Malpighian tubules.
Contractile Vacuoles in Microorganisms
The most fundamental feature of life is the presence of a cell. In other words, a cell is the simplest functional unit of a
life. Bacteria are unicellular, prokaryotic organisms that have some of the least complex life processes in place; however,
prokaryotes such as bacteria do not contain membrane-bound vacuoles. The cells of microorganisms like bacteria, protozoa,
and fungi are bound by cell membranes and use them to interact with the environment. Some cells, including some
leucocytes in humans, are able to engulf food by endocytosis—the formation of vesicles by involution of the cell membrane
within the cells. The same vesicles are able to interact and exchange metabolites with the intracellular environment. In
some unicellular eukaryotic organisms such as the amoeba, shown in Figure 41.9 , cellular wastes and excess water are
excreted by exocytosis, when the contractile vacuoles merge with the cell membrane and expel wastes into the environment.
Contractile vacuoles (CV) should not be confused with vacuoles, which store food or water.
Chapter 41 | Osmotic Regulation and Excretion 1199 Figure 41.9 Some unicellular organisms, such as the amoeba, ingest food by endocytosis. The food vesicle fuses with
a lysosome, which digests the food. Waste is excreted by exocytosis.
Flame Cells of Planaria and Nephridia of Worms
As multi-cellular systems evolved to have organ systems that divided the metabolic needs of the body, individual organs
evolved to perform the excretory function. Planaria are flatworms that live in fresh water. Their excretory system consists of
two tubules connected to a highly branched duct system. The cells in the tubules are called flame cells (or protonephridia )
because they have a cluster of cilia that looks like a flickering flame when viewed under the microscope, as illustrated
in Figure 41.10 a. The cilia propel waste matter down the tubules and out of the body through excretory pores that open
on the body surface; cilia also draw water from the interstitial fluid, allowing for filtration. Any valuable metabolites are
recovered by reabsorption. Flame cells are found in flatworms, including parasitic tapeworms and free-living planaria. They
also maintain the organism’s osmotic balance.
Figure 41.10 In the excretory system of the (a) planaria, cilia of flame cells propel waste through a tubule formed
by a tube cell. Tubules are connected into branched structures that lead to pores located all along the sides of the
body. The filtrate is secreted through these pores. In (b) annelids such as earthworms, nephridia filter fluid from the
coelom, or body cavity. Beating cilia at the opening of the nephridium draw water from the coelom into a tubule. As
the filtrate passes down the tubules, nutrients and other solutes are reabsorbed by capillaries. Filtered fluid containing
nitrogenous and other wastes is stored in a bladder and then secreted through a pore in the side of the body.
Earthworms (annelids) have slightly more evolved excretory structures called nephridia , illustrated in Figure 41.10 b.A
pair of nephridia is present on each segment of the earthworm. They are similar to flame cells in that they have a tubule
with cilia. Excretion occurs through a pore called the nephridiopore . They are more evolved than the flame cells in that
they have a system for tubular reabsorption by a capillary network before excretion.
Malpighian Tubules of Insects
Malpighian tubules are found lining the gut of some species of arthropods, such as the bee illustrated in Figure 41.11 . They
are usually found in pairs and the number of tubules varies with the species of insect. Malpighian tubules are convoluted,
which increases their surface area, and they are lined with microvilli for reabsorption and maintenance of osmotic balance.
Malpighian tubules work cooperatively with specialized glands in the wall of the rectum. Body fluids are not filtered as
in the case of nephridia; urine is produced by tubular secretion mechanisms by the cells lining the Malpighian tubules that
are bathed in hemolymph (a mixture of blood and interstitial fluid that is found in insects and other arthropods as well as
most mollusks). Metabolic wastes like uric acid freely diffuse into the tubules. There are exchange pumps lining the tubules,
which actively transport H +ions into the cell and K +or Na +ions out; water passively follows to form urine. The secretion
1200 Chapter 41 | Osmotic Regulation and Excretion
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 of ions alters the osmotic pressure which draws water, electrolytes, and nitrogenous waste (uric acid) into the tubules. Water
and electrolytes are reabsorbed when these organisms are faced with low-water environments, and uric acid is excreted as a
thick paste or powder. Not dissolving wastes in water helps these organisms to conserve water; this is especially important
for life in dry environments.
Figure 41.11 Malpighian tubules of insects and other terrestrial arthropods remove nitrogenous wastes and other
solutes from the hemolymph. Na +and/or K +ions are actively transported into the lumen of the tubules. Water then
enters the tubules via osmosis, forming urine. The urine passes through the intestine, and into the rectum. There,
nutrients diffuse back into the hemolymph. Na +and/or K +ions are pumped into the hemolymph, and water follows.
The concentrated waste is then excreted.
Visit this site (http://openstaxcollege.org/l/malpighian) to see a dissected cockroach, including a close-up look at its
Malpighian tubules.
41.4 | Nitrogenous Wastes
By the end of this section, you will be able to:
• Compare and contrast the way in which aquatic animals and terrestrial animals can eliminate toxic ammonia from
their systems
• Compare the major byproduct of ammonia metabolism in vertebrate animals to that of birds, insects, and reptiles
Of the four major macromolecules in biological systems, both proteins and nucleic acids contain nitrogen. During the
catabolism, or breakdown, of nitrogen-containing macromolecules, carbon, hydrogen, and oxygen are extracted and stored
in the form of carbohydrates and fats. Excess nitrogen is excreted from the body. Nitrogenous wastes tend to form toxic
ammonia , which raises the pH of body fluids. The formation of ammonia itself requires energy in the form of ATP and
large quantities of water to dilute it out of a biological system. Animals that live in aquatic environments tend to release
ammonia into the water. Animals that excrete ammonia are said to be ammonotelic . Terrestrial organisms have evolved
other mechanisms to excrete nitrogenous wastes. The animals must detoxify ammonia by converting it into a relatively
nontoxic form such as urea or uric acid. Mammals, including humans, produce urea, whereas reptiles and many terrestrial
Chapter 41 | Osmotic Regulation and Excretion 1201 invertebrates produce uric acid. Animals that secrete urea as the primary nitrogenous waste material are called ureotelic
animals.
Nitrogenous Waste in Terrestrial Animals: The Urea Cycle
The urea cycle is the primary mechanism by which mammals convert ammonia to urea. Urea is made in the liver and
excreted in urine. The overall chemical reaction by which ammonia is converted to urea is 2 NH 3(ammonia) + CO 2+3
ATP + H 2O → H 2N-CO-NH 2(urea) + 2 ADP + 4 P i+ AMP.
The urea cycle utilizes five intermediate steps, catalyzed by five different enzymes, to convert ammonia to urea, as shown
inFigure 41.12 . The amino acid L-ornithine gets converted into different intermediates before being regenerated at the end
of the urea cycle. Hence, the urea cycle is also referred to as the ornithine cycle. The enzyme ornithine transcarbamylase
catalyzes a key step in the urea cycle and its deficiency can lead to accumulation of toxic levels of ammonia in the body.
The first two reactions occur in the mitochondria and the last three reactions occur in the cytosol. Urea concentration in the
blood, called blood urea nitrogen or BUN, is used as an indicator of kidney function.
Figure 41.12 The urea cycle converts ammonia to urea.
1202 Chapter 41 | Osmotic Regulation and Excretion
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The theory of evolution proposes that life started in an aquatic environment. It is not surprising to see
that biochemical pathways like the urea cycle evolved to adapt to a changing environment when terrestrial
life forms evolved. Arid conditions probably led to the evolution of the uric acid pathway as a means of
conserving water.
Nitrogenous Waste in Birds and Reptiles: Uric Acid
Birds, reptiles, and most terrestrial arthropods convert toxic ammonia to uric acid or the closely related compound guanine
(guano) instead of urea. Mammals also form some uric acid during breakdown of nucleic acids. Uric acid is a compound
similar to purines found in nucleic acids. It is water insoluble and tends to form a white paste or powder; it is excreted
by birds, insects, and reptiles. Conversion of ammonia to uric acid requires more energy and is much more complex than
conversion of ammonia to urea Figure 41.13 .
Figure 41.13 Nitrogenous waste is excreted in different forms by different species. These include (a) ammonia, (b)
urea, and (c) uric acid. (credit a: modification of work by Eric Engbretson, USFWS; credit b: modification of work by B.
"Moose" Peterson, USFWS; credit c: modification of work by Dave Menke, USFWS)
Chapter 41 | Osmotic Regulation and Excretion 1203 Gout
Mammals use uric acid crystals as an antioxidant in their cells. However, too much uric acid tends to form
kidney stones and may also cause a painful condition called gout, where uric acid crystals accumulate in the
joints, as illustrated in Figure 41.14 . Food choices that reduce the amount of nitrogenous bases in the diet
help reduce the risk of gout. For example, tea, coffee, and chocolate have purine-like compounds, called
xanthines, and should be avoided by people with gout and kidney stones.
Figure 41.14 Gout causes the inflammation visible in this person’s left big toe joint. (credit: "Gonzosft"/Wikimedia
Commons)
41.5 | Hormonal Control of Osmoregulatory Functions
By the end of this section, you will be able to:
• Explain how hormonal cues help the kidneys synchronize the osmotic needs of the body
• Describe how hormones like epinephrine, norepinephrine, renin-angiotensin, aldosterone, anti-diuretic hormone,
and atrial natriuretic peptide help regulate waste elimination, maintain correct osmolarity, and perform other
osmoregulatory functions
While the kidneys operate to maintain osmotic balance and blood pressure in the body, they also act in concert with
hormones. Hormones are small molecules that act as messengers within the body. Hormones are typically secreted from
one cell and travel in the bloodstream to affect a target cell in another portion of the body. Different regions of the nephron
bear specialized cells that have receptors to respond to chemical messengers and hormones. Table 41.1 summarizes the
hormones that control the osmoregulatory functions.
Hormones That Affect Osmoregulation
Hormone Where produced Function
Epinephrine and
Norepinephrine Adrenal medulla Can decrease kidney function temporarily by vasoconstriction
Renin Kidney nephrons Increases blood pressure by acting on angiotensinogen
Table 41.1
1204 Chapter 41 | Osmotic Regulation and Excretion
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Hormone Where produced Function
Angiotensin Liver Angiotensin II affects multiple processes and increases blood
pressure
Aldosterone Adrenal cortex Prevents loss of sodium and water
Anti-diuretic
hormone
(vasopressin)
Hypothalamus (stored
in the posterior
pituitary)
Prevents water loss
Atrial natriuretic
peptide Heart atrium
Decreases blood pressure by acting as a vasodilator and
increasing glomerular filtration rate; decreases sodium
reabsorption in kidneys
Table 41.1
Epinephrine and Norepinephrine
Epinephrine and norepinephrine are released by the adrenal medulla and nervous system respectively. They are the flight/
fight hormones that are released when the body is under extreme stress. During stress, much of the body’s energy is used
to combat imminent danger. Kidney function is halted temporarily by epinephrine and norepinephrine. These hormones
function by acting directly on the smooth muscles of blood vessels to constrict them. Once the afferent arterioles are
constricted, blood flow into the nephrons stops. These hormones go one step further and trigger the renin-angiotensin-
aldosterone system.
Renin-Angiotensin-Aldosterone
The renin-angiotensin-aldosterone system, illustrated in Figure 41.15 proceeds through several steps to produce
angiotensin II , which acts to stabilize blood pressure and volume. Renin (secreted by a part of the juxtaglomerular
complex) is produced by the granular cells of the afferent and efferent arterioles. Thus, the kidneys control blood
pressure and volume directly. Renin acts on angiotensinogen, which is made in the liver and converts it to angiotensin I .
Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II. Angiotensin II raises blood pressure by
constricting blood vessels. It also triggers the release of the mineralocorticoid aldosterone from the adrenal cortex, which in
turn stimulates the renal tubules to reabsorb more sodium. Angiotensin II also triggers the release of anti-diuretic hormone
(ADH) from the hypothalamus, leading to water retention in the kidneys. It acts directly on the nephrons and decreases
glomerular filtration rate. Medically, blood pressure can be controlled by drugs that inhibit ACE (called ACE inhibitors).
Chapter 41 | Osmotic Regulation and Excretion 1205 Figure 41.15 The renin-angiotensin-aldosterone system increases blood pressure and volume. The hormone ANP has
antagonistic effects. (credit: modification of work by Mikael Häggström)
Mineralocorticoids
Mineralocorticoids are hormones synthesized by the adrenal cortex that affect osmotic balance. Aldosterone is a
mineralocorticoid that regulates sodium levels in the blood. Almost all of the sodium in the blood is reclaimed by the renal
tubules under the influence of aldosterone. Because sodium is always reabsorbed by active transport and water follows
sodium to maintain osmotic balance, aldosterone manages not only sodium levels but also the water levels in body fluids.
In contrast, the aldosterone also stimulates potassium secretion concurrently with sodium reabsorption. In contrast, absence
of aldosterone means that no sodium gets reabsorbed in the renal tubules and all of it gets excreted in the urine. In addition,
the daily dietary potassium load is not secreted and the retention of K +can cause a dangerous increase in plasma K +
concentration. Patients who have Addison's disease have a failing adrenal cortex and cannot produce aldosterone. They lose
sodium in their urine constantly, and if the supply is not replenished, the consequences can be fatal.
Antidiurectic Hormone
As previously discussed, antidiuretic hormone or ADH (also called vasopressin ), as the name suggests, helps the body
conserve water when body fluid volume, especially that of blood, is low. It is formed by the hypothalamus and is stored
and released from the posterior pituitary. It acts by inserting aquaporins in the collecting ducts and promotes reabsorption
of water. ADH also acts as a vasoconstrictor and increases blood pressure during hemorrhaging.
Atrial Natriuretic Peptide Hormone
The atrial natriuretic peptide (ANP) lowers blood pressure by acting as a vasodilator . It is released by cells in the atrium
of the heart in response to high blood pressure and in patients with sleep apnea. ANP affects salt release, and because water
passively follows salt to maintain osmotic balance, it also has a diuretic effect. ANP also prevents sodium reabsorption by
the renal tubules, decreasing water reabsorption (thus acting as a diuretic) and lowering blood pressure. Its actions suppress
the actions of aldosterone, ADH, and renin.
1206 Chapter 41 | Osmotic Regulation and Excretion
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ammonia
ammonotelic
angiotensin converting enzyme (ACE)
angiotensin I
angiotensin II
anti-diuretic hormone (ADH)
antioxidant
arcuate artery
ascending limb
blood urea nitrogen (BUN)
Bowman's capsule
calyx
cortex (animal)
cortical nephron
cortical radiate artery
countercurrent exchanger
countercurrent multiplier
descending limb
distal convoluted tubule (DCT)
efferent arteriole
electrolyte
flame cell
glomerular filtration
glomerular filtration rate (GFR)
glomerulus (renal)
hilum
inferior vena cava
interlobar artery
juxtaglomerular cell
juxtamedullary nephron
KEY TERMS
arteriole that branches from the cortical radiate artery and enters the glomerulus
compound made of one nitrogen atom and three hydrogen atoms
describes an animal that excretes ammonia as the primary waste material
enzyme that converts angiotensin I to angiotensin II
product in the renin-angiotensin-aldosterone pathway
molecule that affects different organs to increase blood pressure
hormone that prevents the loss of water
agent that prevents cell destruction by reactive oxygen species
artery that branches from the interlobar artery and arches over the base of the renal pyramids
part of the loop of Henle that ascends from the renal medulla to the renal cortex
estimate of urea in the blood and an indicator of kidney function
structure that encloses the glomerulus
structure that connects the renal pelvis to the renal medulla
outer layer of an organ like the kidney or adrenal gland
nephron that lies in the renal cortex
artery that radiates from the arcuate arteries into the renal cortex
peritubular capillary network that allows exchange of solutes and water from the renal
tubules
osmotic gradient in the renal medulla that is responsible for concentration of urine
part of the loop of Henle that descends from the renal cortex into the renal medulla
part of the renal tubule that is the most distant from the glomerulus
arteriole that exits from the glomerulus
solute that breaks down into ions when dissolved in water
(also, protonephridia) excretory cell found in flatworms
filtration of blood in the glomerular capillary network into the glomerulus
amount of filtrate formed by the glomerulus per minute
part of the renal corpuscle that contains the capillary network
region in the renal pelvis where blood vessels, nerves, and ureters bunch before entering or exiting the kidney
one of the main veins in the human body
artery that branches from the segmental artery and travels in between the renal lobes
cell in the afferent and efferent arterioles that responds to stimuli from the macula densa
nephron that lies in the cortex but close to the renal medulla
Chapter 41 | Osmotic Regulation and Excretion 1207 kidney
lobes of the kidney
loop of Henle
macula densa
Malpighian tubule
medulla
microvilli
molality
molarity
mole
nephridia
nephridiopore
nephron
non-electrolyte
osmoconformer
osmoregulation
osmoregulator
osmotic balance
osmotic pressure
perirenal fat capsule
peritubular capillary network
proximal convoluted tubule (PCT)
renal artery
renal capsule
renal column
renal corpuscle
renal fascia
renal pelvis
renal pyramid
renal tubule
organ that performs excretory and osmoregulatory functions
renal pyramid along with the adjoining cortical region
part of the renal tubule that loops into the renal medulla
group of cells that senses changes in sodium ion concentration; present in parts of the renal tubule and
collecting ducts
excretory tubules found in arthropods
middle layer of an organ like the kidney or adrenal gland
cellular processes that increase the surface area of cells
number of moles of solute per kilogram of solvent
number of moles of solute per liter of solution
gram equivalent of the molecular weight of a substance
excretory structures found in annelids
pore found at the end of nephridia
functional unit of the kidney
solute that does not break down into ions when dissolved in water
organism that changes its tonicity based on its environment
mechanism by which water and solute concentrations are maintained at desired levels
organism that maintains its tonicity irrespective of its environment
balance of the amount of water and salt input and output to and from a biological system without
disturbing the desired osmotic pressure and solute concentration in every compartment
pressure exerted on a membrane to equalize solute concentration on either side
fat layer that suspends the kidneys
capillary network that surrounds the renal tubule after the efferent artery exits the
glomerulus
part of the renal tubule that lies close to the glomerulus
branch of the artery that enters the kidney
layer that encapsulates the kidneys
area of the kidney through which the interlobar arteries travel in the process of supplying blood to the renal
lobes
glomerulus and the Bowman's capsule together
connective tissue that supports the kidneys
region in the kidney where the calyces join the ureters
conical structure in the renal medulla
tubule of the nephron that arises from the glomerulus
1208 Chapter 41 | Osmotic Regulation and Excretion
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renin-angiotensin-aldosterone
segmental artery
semi-permeable membrane
transport maximum
tubular reabsorption
tubular secretion
urea cycle
ureotelic
ureter
uric acid
urinary bladder
urine
vasa recta
vasodilator
vasopressin
branch of a vein that exits the kidney and joins the inferior vena cava
biochemical pathway that activates angiotensin II, which increases blood pressure
artery that branches from the renal artery
membrane that allows only certain solutes to pass through
maximum amount of solute that can be transported out of the renal tubules during reabsorption
reclamation of water and solutes that got filtered out in the glomerulus
process of secretion of wastes that do not get reabsorbed
pathway by which ammonia is converted to urea
describes animals that secrete urea as the primary nitrogenous waste material
urine-bearing tube coming out of the kidney; carries urine to the bladder
byproduct of ammonia metabolism in birds, insects, and reptiles
structure that the ureters empty the urine into; stores urine
filtrate produced by kidneys that gets excreted out of the body
peritubular network that surrounds the loop of Henle of the juxtamedullary nephrons
compound that increases the diameter of blood vessels
another name for anti-diuretic hormone
CHAPTER SUMMARY
41.1 Osmoregulation and Osmotic Balance
Solute concentrations across a semi-permeable membranes influence the movement of water and solutes across the
membrane. It is the number of solute molecules and not the molecular size that is important in osmosis. Osmoregulation
and osmotic balance are important bodily functions, resulting in water and salt balance. Not all solutes can pass through a
semi-permeable membrane. Osmosis is the movement of water across the membrane. Osmosis occurs to equalize the
number of solute molecules across a semi-permeable membrane by the movement of water to the side of higher solute
concentration. Facilitated diffusion utilizes protein channels to move solute molecules from areas of higher to lower
concentration while active transport mechanisms are required to move solutes against concentration gradients. Osmolarity
is measured in units of milliequivalents or milliosmoles, both of which take into consideration the number of solute
particles and the charge on them. Fish that live in fresh water or saltwater adapt by being osmoregulators or
osmoconformers.
41.2 The Kidneys and Osmoregulatory Organs
The kidneys are the main osmoregulatory organs in mammalian systems; they function to filter blood and maintain the
osmolarity of body fluids at 300 mOsm. They are surrounded by three layers and are made up internally of three distinct
regions—the cortex, medulla, and pelvis.
The blood vessels that transport blood into and out of the kidneys arise from and merge with the aorta and inferior vena
cava, respectively. The renal arteries branch out from the aorta and enter the kidney where they further divide into
segmental, interlobar, arcuate, and cortical radiate arteries.
The nephron is the functional unit of the kidney, which actively filters blood and generates urine. The nephron is made up
of the renal corpuscle and renal tubule. Cortical nephrons are found in the renal cortex, while juxtamedullary nephrons are
found in the renal cortex close to the renal medulla. The nephron filters and exchanges water and solutes with two sets of
blood vessels and the tissue fluid in the kidneys.
There are three steps in the formation of urine: glomerular filtration, which occurs in the glomerulus; tubular reabsorption,
which occurs in the renal tubules; and tubular secretion, which also occurs in the renal tubules.
Chapter 41 | Osmotic Regulation and Excretion 1209 41.3 Excretion Systems
Many systems have evolved for excreting wastes that are simpler than the kidney and urinary systems of vertebrate
animals. The simplest system is that of contractile vacuoles present in microorganisms. Flame cells and nephridia in
worms perform excretory functions and maintain osmotic balance. Some insects have evolved Malpighian tubules to
excrete wastes and maintain osmotic balance.
41.4 Nitrogenous Wastes
Ammonia is the waste produced by metabolism of nitrogen-containing compounds like proteins and nucleic acids. While
aquatic animals can easily excrete ammonia into their watery surroundings, terrestrial animals have evolved special
mechanisms to eliminate the toxic ammonia from their systems. Urea is the major byproduct of ammonia metabolism in
vertebrate animals. Uric acid is the major byproduct of ammonia metabolism in birds, terrestrial arthropods, and reptiles.
41.5 Hormonal Control of Osmoregulatory Functions
Hormonal cues help the kidneys synchronize the osmotic needs of the body. Hormones like epinephrine, norepinephrine,
renin-angiotensin, aldosterone, anti-diuretic hormone, and atrial natriuretic peptide help regulate the needs of the body as
well as the communication between the different organ systems.
ART CONNECTION QUESTIONS
1. Figure 41.5 Which of the following statements about
the kidney is false?
a. The renal pelvis drains into the ureter.
b. The renal pyramids are in the medulla.
c. The cortex covers the capsule.
d. Nephrons are in the renal cortex.
2. Figure 41.6 Which of the following statements about
the nephron is false?
a. The collecting duct empties into the distal
convoluted tubule.
b. The Bowman’s capsule surrounds the
glomerulus.
c. The loop of Henle is between the proximal and
distal convoluted tubules.
d. The loop of Henle empties into the distal
convoluted tubule.
3. Figure 41.8 Loop diuretics are drugs sometimes used to
treat hypertension. These drugs inhibit the reabsorption of
Na +and Cl -ions by the ascending limb of the loop of
Henle. A side effect is that they increase urination. Why
do you think this is the case?
REVIEW QUESTIONS
4. When a dehydrated human patient needs to be given
fluids intravenously, he or she is given:
a. water, which is hypotonic with respect to body
fluids
b. saline at a concentration that is isotonic with
respect to body fluids
c. glucose because it is a non-electrolyte
d. blood
5. The sodium ion is at the highest concentration in:
a. intracellular fluid
b. extracellular fluid
c. blood plasma
d. none of the above
6. Cells in a hypertonic solution tend to:
a. shrink due to water loss
b. swell due to water gain
c. stay the same size due to water moving into and
out of the cell at the same rate
d. none of the above
7. The macula densa is/are:
a. present in the renal medulla.
b. dense tissue present in the outer layer of the
kidney.
c. cells present in the DCT and collecting tubules.
d. present in blood capillaries.
8. The osmolarity of body fluids is maintained at
________.
a. 100 mOsm
b. 300 mOsm
c. 1000 mOsm
d. it is not constantly maintained
9. The gland located at the top of the kidney is the
________ gland.
a. adrenal
b. pituitary
c. thyroid
d. thymus
10. Active transport of K +in Malpighian tubules ensures
that:
1210 Chapter 41 | Osmotic Regulation and Excretion
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 a. water follows K +to make urine
b. osmotic balance is maintained between waste
matter and bodily fluids
c. both a and b
d. neither a nor b
11. Contractile vacuoles in microorganisms:
a. exclusively perform an excretory function
b. can perform many functions, one of which is
excretion of metabolic wastes
c. originate from the cell membrane
d. both b and c
12. Flame cells are primitive excretory organs found in
________.
a. arthropods
b. annelids
c. mammals
d. flatworms
13. BUN is ________.
a. blood urea nitrogen
b. blood uric acid nitrogen
c. an indicator of blood volume
d. an indicator of blood pressure
14. Human beings accumulate ________ before excreting
nitrogenous waste.
a. nitrogen
b. ammonia
c. urea
d. uric acid
15. Renin is made by ________.
a. granular cells of the juxtaglomerular apparatus
b. the kidneys
c. the nephrons
d. All of the above.
16. Patients with Addison's disease ________.
a. retain water
b. retain salts
c. lose salts and water
d. have too much aldosterone
17. Which hormone elicits the “fight or flight” response?
a. epinephrine
b. mineralcorticoids
c. anti-diuretic hormone
d. thyroxine
CRITICAL THINKING QUESTIONS
18. Why is excretion important in order to achieve
osmotic balance?
19. Why do electrolyte ions move across membranes by
active transport?
20. Why are the loop of Henle and vasa recta important
for the formation of concentrated urine?
21. Describe the structure of the kidney.
22. Why might specialized organs have evolved for
excretion of wastes?
23. Explain two different excretory systems other than the
kidneys.
24. In terms of evolution, why might the urea cycle have
evolved in organisms?
25. Compare and contrast the formation of urea and uric
acid.
26. Describe how hormones regulate blood pressure,
blood volume, and kidney function.
27. How does the renin-angiotensin-aldosterone
mechanism function? Why is it controlled by the kidneys?
Chapter 41 | Osmotic Regulation and Excretion 1211 1212 Chapter 41 | Osmotic Regulation and Excretion
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 42 | THE IMMUNE SYSTEM
Figure 42.1 In this compound light micrograph purple-stained neutrophil (upper left) and eosinophil (lower right)
are white blood cells that float among red blood cells in this blood smear. Neutrophils provide an early, rapid, and
nonspecific defense against invading pathogens. Eosinophils play a variety of roles in the immune response. Red
blood cells are about 7–8 µm in diameter, and a neutrophil is about 10–12µm. (credit: modification of work by Dr. David
Csaba)
Chapter Outline
42.1: Innate Immune Response
42.2: Adaptive Immune Response
42.3: Antibodies
42.4: Disruptions in the Immune System
Introduction
The environment consists of numerous pathogens , which are agents, usually microorganisms, that cause diseases in their
hosts. A host is the organism that is invaded and often harmed by a pathogen. Pathogens include bacteria, protists, fungi
and other infectious organisms. We are constantly exposed to pathogens in food and water, on surfaces, and in the air.
Mammalian immune systems evolved for protection from such pathogens; they are composed of an extremely diverse
array of specialized cells and soluble molecules that coordinate a rapid and flexible defense system capable of providing
protection from a majority of these disease agents.
Components of the immune system constantly search the body for signs of pathogens. When pathogens are found, immune
factors are mobilized to the site of an infection. The immune factors identify the nature of the pathogen, strengthen the
corresponding cells and molecules to combat it efficiently, and then halt the immune response after the infection is cleared
to avoid unnecessary host cell damage. The immune system can remember pathogens to which it has been exposed to
create a more efficient response upon re-exposure. This memory can last several decades. Features of the immune system,
such as pathogen identification, specific response, amplification, retreat, and remembrance are essential for survival against
pathogens. The immune response can be classified as either innate or active. The innate immune response is always present
and attempts to defend against all pathogens rather than focusing on specific ones. Conversely, the adaptive immune
response stores information about past infections and mounts pathogen-specific defenses.
Chapter 42 | The Immune System 1213 42.1 | Innate Immune Response
By the end of this section, you will be able to:
• Describe physical and chemical immune barriers
• Explain immediate and induced innate immune responses
• Discuss natural killer cells
• Describe major histocompatibility class I molecules
• Summarize how the proteins in a complement system function to destroy extracellular pathogens
The immune system comprises both innate and adaptive immune responses. Innate immunity occurs naturally because of
genetic factors or physiology; it is not induced by infection or vaccination but works to reduce the workload for the adaptive
immune response. Both the innate and adaptive levels of the immune response involve secreted proteins, receptor-mediated
signaling, and intricate cell-to-cell communication. The innate immune system developed early in animal evolution, roughly
a billion years ago, as an essential response to infection. Innate immunity has a limited number of specific targets: any
pathogenic threat triggers a consistent sequence of events that can identify the type of pathogen and either clear the infection
independently or mobilize a highly specialized adaptive immune response. For example, tears and mucus secretions contain
microbicidal factors.
Physical and Chemical Barriers
Before any immune factors are triggered, the skin functions as a continuous, impassable barrier to potentially infectious
pathogens. Pathogens are killed or inactivated on the skin by desiccation (drying out) and by the skin’s acidity. In addition,
beneficial microorganisms that coexist on the skin compete with invading pathogens, preventing infection. Regions of the
body that are not protected by skin (such as the eyes and mucus membranes) have alternative methods of defense, such as
tears and mucus secretions that trap and rinse away pathogens, and cilia in the nasal passages and respiratory tract that push
the mucus with the pathogens out of the body. Throughout the body are other defenses, such as the low pH of the stomach
(which inhibits the growth of pathogens), blood proteins that bind and disrupt bacterial cell membranes, and the process of
urination (which flushes pathogens from the urinary tract).
Despite these barriers, pathogens may enter the body through skin abrasions or punctures, or by collecting on mucosal
surfaces in large numbers that overcome the mucus or cilia. Some pathogens have evolved specific mechanisms that allow
them to overcome physical and chemical barriers. When pathogens do enter the body, the innate immune system responds
with inflammation, pathogen engulfment, and secretion of immune factors and proteins.
Pathogen Recognition
An infection may be intracellular or extracellular, depending on the pathogen. All viruses infect cells and replicate within
those cells (intracellularly), whereas bacteria and other parasites may replicate intracellularly or extracellularly, depending
on the species. The innate immune system must respond accordingly: by identifying the extracellular pathogen and/
or by identifying host cells that have already been infected. When a pathogen enters the body, cells in the blood and
lymph detect the specific pathogen-associated molecular patterns (PAMPs) on the pathogen’s surface. PAMPs are
carbohydrate, polypeptide, and nucleic acid “signatures” that are expressed by viruses, bacteria, and parasites but which
differ from molecules on host cells. The immune system has specific cells, described in Figure 42.2 and shown in Figure
42.3 , with receptors that recognize these PAMPs. A macrophage is a large phagocytic cell that engulfs foreign particles
and pathogens. Macrophages recognize PAMPs via complementary pattern recognition receptors (PRRs) . PRRs are
molecules on macrophages and dendritic cells which are in contact with the external environment. A monocyte is a type
of white blood cell that circulates in the blood and lymph and differentiates into macrophages after it moves into infected
tissue. Dendritic cells bind molecular signatures of pathogens and promote pathogen engulfment and destruction. Toll-like
receptors (TLRs) are a type of PRR that recognizes molecules that are shared by pathogens but distinguishable from host
molecules). TLRs are present in invertebrates as well as vertebrates, and appear to be one of the most ancient components
of the immune system. TLRs have also been identified in the mammalian nervous system.
1214 Chapter 42 | The Immune System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 42.2 The characteristics and location of cells involved in the innate immune system are described. (credit:
modification of work by NIH)
Chapter 42 | The Immune System 1215 Figure 42.3 Cells of the blood include (1) monocytes, (2) lymphocytes, (3) neutrophils, (4) red blood cells, and (5)
platelets. Note the very similar morphologies of the leukocytes (1, 2, 3). (credit: modification of work by Bruce Wetzel,
Harry Schaefer, NCI; scale-bar data from Matt Russell)
Cytokine Release Affect
The binding of PRRs with PAMPs triggers the release of cytokines, which signal that a pathogen is present and needs to
be destroyed along with any infected cells. A cytokine is a chemical messenger that regulates cell differentiation (form and
function), proliferation (production), and gene expression to affect immune responses. At least 40 types of cytokines exist
in humans that differ in terms of the cell type that produces them, the cell type that responds to them, and the changes they
produce. One type cytokine, interferon, is illustrated in Figure 42.4 .
One subclass of cytokines is the interleukin (IL), so named because they mediate interactions between leukocytes (white
blood cells). Interleukins are involved in bridging the innate and adaptive immune responses. In addition to being released
from cells after PAMP recognition, cytokines are released by the infected cells which bind to nearby uninfected cells and
induce those cells to release cytokines, which results in a cytokine burst.
A second class of early-acting cytokines is interferons, which are released by infected cells as a warning to nearby
uninfected cells. One of the functions of an interferon is to inhibit viral replication. They also have other important
functions, such as tumor surveillance. Interferons work by signaling neighboring uninfected cells to destroy RNA and
reduce protein synthesis, signaling neighboring infected cells to undergo apoptosis (programmed cell death), and activating
immune cells.
In response to interferons, uninfected cells alter their gene expression, which increases the cells’ resistance to infection. One
effect of interferon-induced gene expression is a sharply reduced cellular protein synthesis. Virally infected cells produce
more viruses by synthesizing large quantities of viral proteins. Thus, by reducing protein synthesis, a cell becomes resistant
to viral infection.
1216 Chapter 42 | The Immune System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 42.4 Interferons are cytokines that are released by a cell infected with a virus. Response of neighboring cells
to interferon helps stem the infection.
Phagocytosis and Inflammation
The first cytokines to be produced are pro-inflammatory; that is, they encourage inflammation , the localized redness,
swelling, heat, and pain that result from the movement of leukocytes and fluid through increasingly permeable capillaries
to a site of infection. The population of leukocytes that arrives at an infection site depends on the nature of the infecting
pathogen. Both macrophages and dendritic cells engulf pathogens and cellular debris through phagocytosis. A neutrophil
is also a phagocytic leukocyte that engulfs and digests pathogens. Neutrophils, shown in Figure 42.3 , are the most abundant
leukocytes of the immune system. Neutrophils have a nucleus with two to five lobes, and they contain organelles, called
lysosomes, that digest engulfed pathogens. An eosinophil is a leukocyte that works with other eosinophils to surround a
parasite; it is involved in the allergic response and in protection against helminthes (parasitic worms).
Neutrophils and eosinophils are particularly important leukocytes that engulf large pathogens, such as bacteria and fungi.
A mast cell is a leukocyte that produces inflammatory molecules, such as histamine, in response to large pathogens. A
basophil is a leukocyte that, like a neutrophil, releases chemicals to stimulate the inflammatory response as illustrated
in Figure 42.5 . Basophils are also involved in allergy and hypersensitivity responses and induce specific types of
inflammatory responses. Eosinophils and basophils produce additional inflammatory mediators to recruit more leukocytes.
A hypersensitive immune response to harmless antigens, such as in pollen, often involves the release of histamine by
basophils and mast cells.
Figure 42.5 In response to a cut, mast cells secrete histamines that cause nearby capillaries to dilate. Neutrophils and
monocytes leave the capillaries. Monocytes mature into macrophages. Neutrophils, dendritic cells and macrophages
release chemicals to stimulate the inflammatory response. Neutrophils and macrophages also consume invading
bacteria by phagocytosis.
Chapter 42 | The Immune System 1217 Cytokines also send feedback to cells of the nervous system to bring about the overall symptoms of feeling sick, which
include lethargy, muscle pain, and nausea. These effects may have evolved because the symptoms encourage the individual
to rest and prevent them from spreading the infection to others. Cytokines also increase the core body temperature, causing
a fever, which causes the liver to withhold iron from the blood. Without iron, certain pathogens, such as some bacteria, are
unable to replicate; this is called nutritional immunity.
Watch this 23-second stop-motion video (http://openstaxcollege.org/l/conidia) showing a neutrophil that searches for
and engulfs fungus spores during an elapsed time of about 79 minutes.
Natural Killer Cells
Lymphocytes are leukocytes that are histologically identifiable by their large, darkly staining nuclei; they are small cells
with very little cytoplasm, as shown in Figure 42.6 . Infected cells are identified and destroyed by natural killer (NK) cells ,
lymphocytes that can kill cells infected with viruses or tumor cells (abnormal cells that uncontrollably divide and invade
other tissue). T cells and B cells of the adaptive immune system also are classified as lymphocytes. Tcells are lymphocytes
that mature in the thymus gland, and Bcells are lymphocytes that mature in the bone marrow. NK cells identify intracellular
infections, especially from viruses, by the altered expression of major histocompatibility class (MHC) I molecules on
the surface of infected cells. MHC I molecules are proteins on the surfaces of all nucleated cells, thus they are scarce on
red blood cells and platelets which are non-nucleated. The function of MHC I molecules is to display fragments of proteins
from the infectious agents within the cell to T-cells; healthy cells will be ignored, while “non-self” or foreign proteins will
be attacked by the immune system. MHC II molecules are found mainly on cells containing antigens (“non-self proteins”)
and on lymphocytes. MHC II molecules interact with helper T-cells to trigger the appropriate immune response, which
may include the inflammatory response.
Figure 42.6 Lymphocytes, such as
cells, are characterized by their large nuclei that actively absorb Wright stain
and therefore appear dark colored under a microscope.
An infected cell (or a tumor cell) is usually incapable of synthesizing and displaying MHC I molecules appropriately.
The metabolic resources of cells infected by some viruses produce proteins that interfere with MHC I processing and/
or trafficking to the cell surface. The reduced MHC I on host cells varies from virus to virus and results from active
inhibitors being produced by the viruses. This process can deplete host MHC I molecules on the cell surface, which NK
cells detect as “unhealthy” or “abnormal” while searching for cellular MHC I molecules. Similarly, the dramatically altered
1218 Chapter 42 | The Immune System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 gene expression of tumor cells leads to expression of extremely deformed or absent MHC I molecules that also signal
“unhealthy” or “abnormal.”
NK cells are always active; an interaction with normal, intact MHC I molecules on a healthy cell disables the killing
sequence, and the NK cell moves on. After the NK cell detects an infected or tumor cell, its cytoplasm secretes granules
comprised of perforin , a destructive protein that creates a pore in the target cell. Granzymes are released along with the
perforin in the immunological synapse. A granzyme is a protease that digests cellular proteins and induces the target cell to
undergo programmed cell death, or apoptosis. Phagocytic cells then digest the cell debris left behind. NK cells are constantly
patrolling the body and are an effective mechanism for controlling potential infections and preventing cancer progression.
Complement
An array of approximately 20 types of soluble proteins, called a complement system , functions to destroy extracellular
pathogens. Cells of the liver and macrophages synthesize complement proteins continuously; these proteins are abundant
in the blood serum and are capable of responding immediately to infecting microorganisms. The complement system is so
named because it is complementary to the antibody response of the adaptive immune system. Complement proteins bind
to the surfaces of microorganisms and are particularly attracted to pathogens that are already bound by antibodies. Binding
of complement proteins occurs in a specific and highly regulated sequence, with each successive protein being activated
by cleavage and/or structural changes induced upon binding of the preceding protein(s). After the first few complement
proteins bind, a cascade of sequential binding events follows in which the pathogen rapidly becomes coated in complement
proteins.
Complement proteins perform several functions. The proteins serve as a marker to indicate the presence of a pathogen to
phagocytic cells, such as macrophages and B cells, and enhance engulfment; this process is called opsonization . Certain
complement proteins can combine to form attack complexes that open pores in microbial cell membranes. These structures
destroy pathogens by causing their contents to leak, as illustrated in Figure 42.7 .
Chapter 42 | The Immune System 1219 Figure 42.7 The classic pathway for the complement cascade involves the attachment of several initial complement
proteins to an antibody-bound pathogen followed by rapid activation and binding of many more complement proteins
and the creation of destructive pores in the microbial cell envelope and cell wall. The alternate pathway does not
involve antibody activation. Rather, C3 convertase spontaneously breaks down C3. Endogenous regulatory proteins
prevent the complement complex from binding to host cells. Pathogens lacking these regulatory proteins are lysed.
(credit: modification of work by NIH)
1220 Chapter 42 | The Immune System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 42.2 | Adaptive Immune Response
By the end of this section, you will be able to:
• Explain adaptive immunity
• Compare and contrast adaptive and innate immunity
• Describe cell-mediated immune response and humoral immune response
• Describe immune tolerance
The adaptive, or acquired, immune response takes days or even weeks to become established—much longer than the
innate response; however, adaptive immunity is more specific to pathogens and has memory. Adaptive immunity is an
immunity that occurs after exposure to an antigen either from a pathogen or a vaccination. This part of the immune system
is activated when the innate immune response is insufficient to control an infection. In fact, without information from the
innate immune system, the adaptive response could not be mobilized. There are two types of adaptive responses: the cell-
mediated immune response , which is carried out by T cells, and the humoral immune response , which is controlled by
activated B cells and antibodies. Activated T cells and B cells that are specific to molecular structures on the pathogen
proliferate and attack the invading pathogen. Their attack can kill pathogens directly or secrete antibodies that enhance
the phagocytosis of pathogens and disrupt the infection. Adaptive immunity also involves a memory to provide the host
with long-term protection from reinfection with the same type of pathogen; on re-exposure, this memory will facilitate an
efficient and quick response.
Antigen-presenting Cells
Unlike NK cells of the innate immune system, B cells (B lymphocytes) are a type of white blood cell that gives rise to
antibodies, whereas T cells (T lymphocytes) are a type of white blood cell that plays an important role in the immune
response. T cells are a key component in the cell-mediated response—the specific immune response that utilizes T cells to
neutralize cells that have been infected with viruses and certain bacteria. There are three types of T cells: cytotoxic, helper,
and suppressor T cells. Cytotoxic T cells destroy virus-infected cells in the cell-mediated immune response, and helper T
cells play a part in activating both the antibody and the cell-mediated immune responses. Suppressor T cells deactivate T
cells and B cells when needed, and thus prevent the immune response from becoming too intense.
An antigen is a foreign or “non-self” macromolecule that reacts with cells of the immune system. Not all antigens will
provoke a response. For instance, individuals produce innumerable “self” antigens and are constantly exposed to harmless
foreign antigens, such as food proteins, pollen, or dust components. The suppression of immune responses to harmless
macromolecules is highly regulated and typically prevents processes that could be damaging to the host, known as tolerance.
The innate immune system contains cells that detect potentially harmful antigens, and then inform the adaptive immune
response about the presence of these antigens. An antigen-presenting cell (APC) is an immune cell that detects, engulfs,
and informs the adaptive immune response about an infection. When a pathogen is detected, these APCs will phagocytose
the pathogen and digest it to form many different fragments of the antigen. Antigen fragments will then be transported to
the surface of the APC, where they will serve as an indicator to other immune cells. Dendritic cells are immune cells that
process antigen material; they are present in the skin (Langerhans cells) and the lining of the nose, lungs, stomach, and
intestines. Sometimes a dendritic cell presents on the surface of other cells to induce an immune response, thus functioning
as an antigen-presenting cell. Macrophages also function as APCs. Before activation and differentiation, B cells can also
function as APCs.
After phagocytosis by APCs, the phagocytic vesicle fuses with an intracellular lysosome forming phagolysosome. Within
the phagolysosome, the components are broken down into fragments; the fragments are then loaded onto MHC class I or
MHC class II molecules and are transported to the cell surface for antigen presentation, as illustrated in Figure 42.8 . Note
that T lymphocytes cannot properly respond to the antigen unless it is processed and embedded in an MHC II molecule.
APCs express MHC on their surfaces, and when combined with a foreign antigen, these complexes signal a “non-self”
invader. Once the fragment of antigen is embedded in the MHC II molecule, the immune cell can respond. Helper T- cells
are one of the main lymphocytes that respond to antigen-presenting cells. Recall that all other nucleated cells of the body
expressed MHC I molecules, which signal “healthy” or “normal.”
Chapter 42 | The Immune System 1221 Figure 42.8 An APC, such as a macrophage, engulfs and digests a foreign bacterium. An antigen from the bacterium
is presented on the cell surface in conjunction with an MHC II molecule Lymphocytes of the adaptive immune response
interact with antigen-embedded MHC II molecules to mature into functional immune cells.
This animation (http://openstaxcollege.org/l/immune_system) from Rockefeller University shows how dendritic cells
act as sentinels in the body's immune system.
T and B Lymphocytes
Lymphocytes in human circulating blood are approximately 80 to 90 percent T cells, shown in Figure 42.9 , and 10 to 20
percent B cells. Recall that the T cells are involved in the cell-mediated immune response, whereas B cells are part of the
humoral immune response.
T cells encompass a heterogeneous population of cells with extremely diverse functions. Some T cells respond to APCs of
the innate immune system, and indirectly induce immune responses by releasing cytokines. Other T cells stimulate B cells
to prepare their own response. Another population of T cells detects APC signals and directly kills the infected cells. Other
T cells are involved in suppressing inappropriate immune reactions to harmless or “self” antigens.
1222 Chapter 42 | The Immune System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 42.9 This scanning electron micrograph shows a T lymphocyte, which is responsible for the cell-mediated
immune response. T cells are able to recognize antigens. (credit: modification of work by NCI; scale-bar data from Matt
Russell)
T and B cells exhibit a common theme of recognition/binding of specific antigens via a complementary receptor, followed
by activation and self-amplification/maturation to specifically bind to the particular antigen of the infecting pathogen. T
and B lymphocytes are also similar in that each cell only expresses one type of antigen receptor. Any individual may
possess a population of T and B cells that together express a near limitless variety of antigen receptors that are capable of
recognizing virtually any infecting pathogen. T and B cells are activated when they recognize small components of antigens,
called epitopes , presented by APCs, illustrated in Figure 42.10 . Note that recognition occurs at a specific epitope rather
than on the entire antigen; for this reason, epitopes are known as “antigenic determinants.” In the absence of information
from APCs, T and B cells remain inactive, or naïve, and are unable to prepare an immune response. The requirement for
information from the APCs of innate immunity to trigger B cell or T cell activation illustrates the essential nature of the
innate immune response to the functioning of the entire immune system.
Figure 42.10 An antigen is a macromolecule that reacts with components of the immune system. A given antigen may
contain several motifs that are recognized by immune cells. Each motif is an epitope. In this figure, the entire structure
is an antigen, and the orange, salmon and green components projecting from it represent potential epitopes.
Naïve T cells can express one of two different molecules, CD4 or CD8, on their surface, as shown in Figure 42.11 , and
are accordingly classified as CD4 +or CD8 +cells. These molecules are important because they regulate how a T cell will
interact with and respond to an APC. Naïve CD4 +cells bind APCs via their antigen-embedded MHC II molecules and
are stimulated to become helper T (T H) lymphocytes , cells that go on to stimulate B cells (or cytotoxic T cells) directly
or secrete cytokines to inform more and various target cells about the pathogenic threat. In contrast, CD8 +cells engage
antigen-embedded MHC I molecules on APCs and are stimulated to become cytotoxic T lymphocytes (CTLs) , which
directly kill infected cells by apoptosis and emit cytokines to amplify the immune response. The two populations of T cells
have different mechanisms of immune protection, but both bind MHC molecules via their antigen receptors called T cell
receptors (TCRs). The CD4 or CD8 surface molecules differentiate whether the TCR will engage an MHC II or an MHC I
molecule. Because they assist in binding specificity, the CD4 and CD8 molecules are described as coreceptors.
Chapter 42 | The Immune System 1223 Figure 42.11 Naïve CD4 +T cells engage MHC II molecules on antigen-presenting cells (APCs) and become
activated. Clones of the activated helper T cell, in turn, activate B cells and CD8 +T cells, which become cytotoxic
T cells. Cytotoxic T cells kill infected cells.
Which of the following statements about T cells is false?
a. Helper T cells release cytokines while cytotoxic T cells kill the infected cell.
b. Helper T cells are CD4 +, while cytotoxic T cells are CD8 +.
c. MHC II is a receptor found on most body cells, while MHC I is a receptor found on immune cells only.
d. The T cell receptor is found on both CD4 +and CD8 +T cells.
Consider the innumerable possible antigens that an individual will be exposed to during a lifetime. The mammalian adaptive
immune system is adept in responding appropriately to each antigen. Mammals have an enormous diversity of T cell
populations, resulting from the diversity of TCRs. Each TCR consists of two polypeptide chains that span the T cell
membrane, as illustrated in Figure 42.12 ; the chains are linked by a disulfide bridge. Each polypeptide chain is comprised of
a constant domain and a variable domain: a domain, in this sense, is a specific region of a protein that may be regulatory or
structural. The intracellular domain is involved in intracellular signaling. A single T cell will express thousands of identical
copies of one specific TCR variant on its cell surface. The specificity of the adaptive immune system occurs because it
synthesizes millions of different T cell populations, each expressing a TCR that differs in its variable domain. This TCR
diversity is achieved by the mutation and recombination of genes that encode these receptors in stem cell precursors of
T cells. The binding between an antigen-displaying MHC molecule and a complementary TCR “match” indicates that the
adaptive immune system needs to activate and produce that specific T cell because its structure is appropriate to recognize
and destroy the invading pathogen.
1224 Chapter 42 | The Immune System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 42.12 A T cell receptor spans the membrane and projects variable binding regions into the extracellular space
to bind processed antigens via MHC molecules on APCs.
Helper T Lymphocytes
The T Hlymphocytes function indirectly to identify potential pathogens for other cells of the immune system. These cells
are important for extracellular infections, such as those caused by certain bacteria, helminths, and protozoa. T Hlymphocytes
recognize specific antigens displayed in the MHC II complexes of APCs. There are two major populations of T Hcells:
TH1 and T H2. T H1 cells secrete cytokines to enhance the activities of macrophages and other T cells. T H1 cells activate
the action of cyotoxic T cells, as well as macrophages. T H2 cells stimulate naïve B cells to destroy foreign invaders via
antibody secretion. Whether a T H1 or a T H2 immune response develops depends on the specific types of cytokines secreted
by cells of the innate immune system, which in turn depends on the nature of the invading pathogen.
The T H1-mediated response involves macrophages and is associated with inflammation. Recall the frontline defenses of
macrophages involved in the innate immune response. Some intracellular bacteria, such as Mycobacterium tuberculosis ,
have evolved to multiply in macrophages after they have been engulfed. These pathogens evade attempts by macrophages to
destroy and digest the pathogen. When M. tuberculosis infection occurs, macrophages can stimulate naïve T cells to become
TH1 cells. These stimulated T cells secrete specific cytokines that send feedback to the macrophage to stimulate its digestive
capabilities and allow it to destroy the colonizing M. tuberculosis . In the same manner, T H1-activated macrophages also
become better suited to ingest and kill tumor cells. In summary; T H1 responses are directed toward intracellular invaders
while T H2 responses are aimed at those that are extracellular.
B Lymphocytes
When stimulated by the T H2 pathway, naïve B cells differentiate into antibody-secreting plasma cells. A plasma cell
is an immune cell that secrets antibodies; these cells arise from B cells that were stimulated by antigens. Similar to T
cells, naïve B cells initially are coated in thousands of B cell receptors (BCRs), which are membrane-bound forms of Ig
(immunoglobulin, or an antibody). The B cell receptor has two heavy chains and two light chains connected by disulfide
linkages. Each chain has a constant and a variable region; the latter is involved in antigen binding. Two other membrane
proteins, Ig alpha and Ig beta, are involved in signaling. The receptors of any particular B cell, as shown in Figure 42.13
are all the same, but the hundreds of millions of different B cells in an individual have distinct recognition domains that
contribute to extensive diversity in the types of molecular structures to which they can bind. In this state, B cells function
as APCs. They bind and engulf foreign antigens via their BCRs and then display processed antigens in the context of MHC
II molecules to T H2 cells. When a T H2 cell detects that a B cell is bound to a relevant antigen, it secretes specific cytokines
that induce the B cell to proliferate rapidly, which makes thousands of identical (clonal) copies of it, and then it synthesizes
and secretes antibodies with the same antigen recognition pattern as the BCRs. The activation of B cells corresponding
to one specific BCR variant and the dramatic proliferation of that variant is known as clonal selection . This phenomenon
drastically, but briefly, changes the proportions of BCR variants expressed by the immune system, and shifts the balance
toward BCRs specific to the infecting pathogen.
Chapter 42 | The Immune System 1225 Figure 42.13 B cell receptors are embedded in the membranes of B cells and bind a variety of antigens through their
variable regions. The signal transduction region transfers the signal into the cell.
T and B cells differ in one fundamental way: whereas T cells bind antigens that have been digested and embedded in MHC
molecules by APCs, B cells function as APCs that bind intact antigens that have not been processed. Although T and B
cells both react with molecules that are termed “antigens,” these lymphocytes actually respond to very different types of
molecules. B cells must be able to bind intact antigens because they secrete antibodies that must recognize the pathogen
directly, rather than digested remnants of the pathogen. Bacterial carbohydrate and lipid molecules can activate B cells
independently from the T cells.
Cytotoxic T Lymphocytes
CTLs, a subclass of T cells, function to clear infections directly. The cell-mediated part of the adaptive immune system
consists of CTLs that attack and destroy infected cells. CTLs are particularly important in protecting against viral
infections; this is because viruses replicate within cells where they are shielded from extracellular contact with circulating
antibodies. When APCs phagocytize pathogens and present MHC I-embedded antigens to naïve CD8 +T cells that express
complementary TCRs, the CD8 +T cells become activated to proliferate according to clonal selection. These resulting CTLs
then identify non-APCs displaying the same MHC I-embedded antigens (for example, viral proteins)—for example, the
CTLs identify infected host cells.
Intracellularly, infected cells typically die after the infecting pathogen replicates to a sufficient concentration and lyses the
cell, as many viruses do. CTLs attempt to identify and destroy infected cells before the pathogen can replicate and escape,
thereby halting the progression of intracellular infections. CTLs also support NK lymphocytes to destroy early cancers.
Cytokines secreted by the T H1 response that stimulates macrophages also stimulate CTLs and enhance their ability to
identify and destroy infected cells and tumors.
CTLs sense MHC I-embedded antigens by directly interacting with infected cells via their TCRs. Binding of TCRs with
antigens activates CTLs to release perforin and granzyme, degradative enzymes that will induce apoptosis of the infected
cell. Recall that this is a similar destruction mechanism to that used by NK cells. In this process, the CTL does not become
infected and is not harmed by the secretion of perforin and granzymes. In fact, the functions of NK cells and CTLs are
complementary and maximize the removal of infected cells, as illustrated in Figure 42.14 . If the NK cell cannot identify
the “missing self” pattern of down-regulated MHC I molecules, then the CTL can identify it by the complex of MHC I
with foreign antigens, which signals “altered self.” Similarly, if the CTL cannot detect antigen-embedded MHC I because
the receptors are depleted from the cell surface, NK cells will destroy the cell instead. CTLs also emit cytokines, such as
interferons, that alter surface protein expression in other infected cells, such that the infected cells can be easily identified
and destroyed. Moreover, these interferons can also prevent virally infected cells from releasing virus particles.
1226 Chapter 42 | The Immune System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 42.14 Natural killer (
) cells recognize the MHC I receptor on healthy cells. If MHC I is absent, the cell is
lysed.
Based on what you know about MHC receptors, why do you think an organ transplanted from an
incompatible donor to a recipient will be rejected?
Plasma cells and CTLs are collectively called effector cells : they represent differentiated versions of their naïve
counterparts, and they are involved in bringing about the immune defense of killing pathogens and infected host cells.
Mucosal Surfaces and Immune Tolerance
The innate and adaptive immune responses discussed thus far comprise the systemic immune system (affecting the
whole body), which is distinct from the mucosal immune system. Mucosal immunity is formed by mucosa-associated
lymphoid tissue, which functions independently of the systemic immune system, and which has its own innate and adaptive
components. Mucosa-associated lymphoid tissue (MALT) , illustrated in Figure 42.15 , is a collection of lymphatic tissue
that combines with epithelial tissue lining the mucosa throughout the body. This tissue functions as the immune barrier and
response in areas of the body with direct contact to the external environment. The systemic and mucosal immune systems
use many of the same cell types. Foreign particles that make their way to MALT are taken up by absorptive epithelial cells
called M cells and delivered to APCs located directly below the mucosal tissue. M cells function in the transport described,
and are located in the Peyer’s patch, a lymphoid nodule. APCs of the mucosal immune system are primarily dendritic cells,
with B cells and macrophages having minor roles. Processed antigens displayed on APCs are detected by T cells in the
MALT and at various mucosal induction sites, such as the tonsils, adenoids, appendix, or the mesenteric lymph nodes of the
intestine. Activated T cells then migrate through the lymphatic system and into the circulatory system to mucosal sites of
infection.
Chapter 42 | The Immune System 1227 Figure 42.15 The topology and function of intestinal MALT is shown. Pathogens are taken up by M cells in the intestinal
epithelium and excreted into a pocket formed by the inner surface of the cell. The pocket contains antigen-presenting
cells such as dendritic cells, which engulf the antigens, then present them with MHC II molecules on the cell surface.
The dendritic cells migrate to an underlying tissue called a Peyer’s patch. Antigen-presenting cells, T cells, and B cells
aggregate within the Peyer’s patch, forming organized lymphoid follicles. There, some T cells and B cells are activated.
Other antigen-loaded dendritic cells migrate through the lymphatic system where they activate B cells, T cells, and
plasma cells in the lymph nodes. The activated cells then return to MALT tissue effector sites. IgA and other antibodies
are secreted into the intestinal lumen.
MALT is a crucial component of a functional immune system because mucosal surfaces, such as the nasal passages, are the
first tissues onto which inhaled or ingested pathogens are deposited. The mucosal tissue includes the mouth, pharynx, and
esophagus, and the gastrointestinal, respiratory, and urogenital tracts.
The immune system has to be regulated to prevent wasteful, unnecessary responses to harmless substances, and more
importantly so that it does not attack “self.” The acquired ability to prevent an unnecessary or harmful immune response
to a detected foreign substance known not to cause disease is described as immune tolerance . Immune tolerance is crucial
for maintaining mucosal homeostasis given the tremendous number of foreign substances (such as food proteins) that APCs
of the oral cavity, pharynx, and gastrointestinal mucosa encounter. Immune tolerance is brought about by specialized APCs
in the liver, lymph nodes, small intestine, and lung that present harmless antigens to an exceptionally diverse population of
regulatory T (T reg )cells , specialized lymphocytes that suppress local inflammation and inhibit the secretion of stimulatory
immune factors. The combined result of T reg cells is to prevent immunologic activation and inflammation in undesired
tissue compartments and to allow the immune system to focus on pathogens instead. In addition to promoting immune
tolerance of harmless antigens, other subsets of T reg cells are involved in the prevention of the autoimmune response ,
which is an inappropriate immune response to host cells or self-antigens. Another T reg class suppresses immune responses
to harmful pathogens after the infection has cleared to minimize host cell damage induced by inflammation and cell lysis.
1228 Chapter 42 | The Immune System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Immunological Memory
The adaptive immune system possesses a memory component that allows for an efficient and dramatic response upon
reinvasion of the same pathogen. Memory is handled by the adaptive immune system with little reliance on cues from the
innate response. During the adaptive immune response to a pathogen that has not been encountered before, called a primary
response, plasma cells secreting antibodies and differentiated T cells increase, then plateau over time. As B and T cells
mature into effector cells, a subset of the naïve populations differentiates into B and T memory cells with the same antigen
specificities, as illustrated in Figure 42.16 .
Amemory cell is an antigen-specific B or T lymphocyte that does not differentiate into effector cells during the primary
immune response, but that can immediately become effector cells upon re-exposure to the same pathogen. During the
primary immune response, memory cells do not respond to antigens and do not contribute to host defenses. As the infection
is cleared and pathogenic stimuli subside, the effectors are no longer needed, and they undergo apoptosis. In contrast, the
memory cells persist in the circulation.
Figure 42.16 After initially binding an antigen to the B cell receptor (BCR), a B cell internalizes the antigen and
presents it on MHC II. A helper T cell recognizes the MHC II–antigen complex and activates the B cell. As a result,
memory B cells and plasma cells are made.
The Rh antigen is found on Rh-positive red blood cells. An Rh-negative female can usually carry an Rh-
positive fetus to term without difficulty. However, if she has a second Rh-positive fetus, her body may launch
an immune attack that causes hemolytic disease of the newborn. Why do you think hemolytic disease is
only a problem during the second or subsequent pregnancies?
Chapter 42 | The Immune System 1229 If the pathogen is never encountered again during the individual’s lifetime, B and T memory cells will circulate for a few
years or even several decades and will gradually die off, having never functioned as effector cells. However, if the host is
re-exposed to the same pathogen type, circulating memory cells will immediately differentiate into plasma cells and CTLs
without input from APCs or T Hcells. One reason the adaptive immune response is delayed is because it takes time for naïve
B and T cells with the appropriate antigen specificities to be identified and activated. Upon reinfection, this step is skipped,
and the result is a more rapid production of immune defenses. Memory B cells that differentiate into plasma cells output tens
to hundreds-fold greater antibody amounts than were secreted during the primary response, as the graph in Figure 42.17
illustrates. This rapid and dramatic antibody response may stop the infection before it can even become established, and the
individual may not realize they had been exposed.
Figure 42.17 In the primary response to infection, antibodies are secreted first from plasma cells. Upon re-exposure
to the same pathogen, memory cells differentiate into antibody-secreting plasma cells that output a greater amount of
antibody for a longer period of time.
Vaccination is based on the knowledge that exposure to noninfectious antigens, derived from known pathogens, generates
a mild primary immune response. The immune response to vaccination may not be perceived by the host as illness but still
confers immune memory. When exposed to the corresponding pathogen to which an individual was vaccinated, the reaction
is similar to a secondary exposure. Because each reinfection generates more memory cells and increased resistance to the
pathogen, and because some memory cells die, certain vaccine courses involve one or more booster vaccinations to mimic
repeat exposures: for instance, tetanus boosters are necessary every ten years because the memory cells only live that long.
Mucosal Immune Memory
A subset of T and B cells of the mucosal immune system differentiates into memory cells just as in the systemic immune
system. Upon reinvasion of the same pathogen type, a pronounced immune response occurs at the mucosal site where the
original pathogen deposited, but a collective defense is also organized within interconnected or adjacent mucosal tissue. For
instance, the immune memory of an infection in the oral cavity would also elicit a response in the pharynx if the oral cavity
was exposed to the same pathogen.
1230 Chapter 42 | The Immune System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Vaccinologist
Vaccination (or immunization) involves the delivery, usually by injection as shown in Figure 42.18 , of
noninfectious antigen(s) derived from known pathogens. Other components, called adjuvants, are delivered
in parallel to help stimulate the immune response. Immunological memory is the reason vaccines work.
Ideally, the effect of vaccination is to elicit immunological memory, and thus resistance to specific pathogens
without the individual having to experience an infection.
Figure 42.18 Vaccines are often delivered by injection into the arm. (credit: U.S. Navy Photographer's Mate
Airman Apprentice Christopher D. Blachly)
Vaccinologists are involved in the process of vaccine development from the initial idea to the availability
of the completed vaccine. This process can take decades, can cost millions of dollars, and can involve
many obstacles along the way. For instance, injected vaccines stimulate the systemic immune system,
eliciting humoral and cell-mediated immunity, but have little effect on the mucosal response, which presents
a challenge because many pathogens are deposited and replicate in mucosal compartments, and the
injection does not provide the most efficient immune memory for these disease agents. For this reason,
vaccinologists are actively involved in developing new vaccines that are applied via intranasal, aerosol,
oral, or transcutaneous (absorbed through the skin) delivery methods. Importantly, mucosal-administered
vaccines elicit both mucosal and systemic immunity and produce the same level of disease resistance as
injected vaccines.
Chapter 42 | The Immune System 1231 Figure 42.19 The polio vaccine can be administered orally. (credit: modification of work by UNICEF Sverige)
Currently, a version of intranasal influenza vaccine is available, and the polio and typhoid vaccines can
be administered orally, as shown in Figure 42.19 . Similarly, the measles and rubella vaccines are being
adapted to aerosol delivery using inhalation devices. Eventually, transgenic plants may be engineered to
produce vaccine antigens that can be eaten to confer disease resistance. Other vaccines may be adapted
to rectal or vaginal application to elicit immune responses in rectal, genitourinary, or reproductive mucosa.
Finally, vaccine antigens may be adapted to transdermal application in which the skin is lightly scraped
and microneedles are used to pierce the outermost layer. In addition to mobilizing the mucosal immune
response, this new generation of vaccines may end the anxiety associated with injections and, in turn,
improve patient participation.
Primary Centers of the Immune System
Although the immune system is characterized by circulating cells throughout the body, the regulation, maturation, and
intercommunication of immune factors occur at specific sites. The blood circulates immune cells, proteins, and other factors
through the body. Approximately 0.1 percent of all cells in the blood are leukocytes, which encompass monocytes (the
precursor of macrophages) and lymphocytes. The majority of cells in the blood are erythrocytes (red blood cells). Lymph is
a watery fluid that bathes tissues and organs with protective white blood cells and does not contain erythrocytes. Cells of the
immune system can travel between the distinct lymphatic and blood circulatory systems, which are separated by interstitial
space, by a process called extravasation (passing through to surrounding tissue).
The cells of the immune system originate from hematopoietic stem cells in the bone marrow. Cytokines stimulate these
stem cells to differentiate into immune cells. B cell maturation occurs in the bone marrow, whereas naïve T cells transit
from the bone marrow to the thymus for maturation. In the thymus, immature T cells that express TCRs complementary to
self-antigens are destroyed. This process helps prevent autoimmune responses.
On maturation, T and B lymphocytes circulate to various destinations. Lymph nodes scattered throughout the body, as
illustrated in Figure 42.20 , house large populations of T and B cells, dendritic cells, and macrophages. Lymph gathers
antigens as it drains from tissues. These antigens then are filtered through lymph nodes before the lymph is returned
to circulation. APCs in the lymph nodes capture and process antigens and inform nearby lymphocytes about potential
pathogens.
1232 Chapter 42 | The Immune System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 42.20 (a) Lymphatic vessels carry a clear fluid called lymph throughout the body. The liquid enters (b) lymph
nodes through afferent vessels. Lymph nodes are filled with lymphocytes that purge infecting cells. The lymph then
exits through efferent vessels. (credit: modification of work by NIH, NCI)
The spleen houses B and T cells, macrophages, dendritic cells, and NK cells. The spleen, shown in Figure 42.21 , is the site
where APCs that have trapped foreign particles in the blood can communicate with lymphocytes. Antibodies are synthesized
and secreted by activated plasma cells in the spleen, and the spleen filters foreign substances and antibody-complexed
pathogens from the blood. Functionally, the spleen is to the blood as lymph nodes are to the lymph.
Figure 42.21 The spleen is similar to a lymph node but is much larger and filters blood instead of lymph. Blood enters
the spleen through arteries and exits through veins. The spleen contains two types of tissue: red pulp and white
pulp. Red pulp consists of cavities that store blood. Within the red pulp, damaged red blood cells are removed and
replaced by new ones. White pulp is rich in lymphocytes that remove antigen-coated bacteria from the blood. (credit:
modification of work by NCI)
Chapter 42 | The Immune System 1233 42.3 | Antibodies
By the end of this section, you will be able to:
• Explain cross-reactivity
• Describe the structure and function of antibodies
• Discuss antibody production
An antibody , also known as an immunoglobulin (Ig), is a protein that is produced by plasma cells after stimulation by
an antigen. Antibodies are the functional basis of humoral immunity. Antibodies occur in the blood, in gastric and mucus
secretions, and in breast milk. Antibodies in these bodily fluids can bind pathogens and mark them for destruction by
phagocytes before they can infect cells.
Antibody Structure
An antibody molecule is comprised of four polypeptides: two identical heavy chains (large peptide units) that are partially
bound to each other in a “Y” formation, which are flanked by two identical light chains (small peptide units), as illustrated in
Figure 42.22 . Bonds between the cysteine amino acids in the antibody molecule attach the polypeptides to each other. The
areas where the antigen is recognized on the antibody are variable domains and the antibody base is composed of constant
domains.
In germ-line B cells, the variable region of the light chain gene has 40 variable (V) and five joining (J) segments. An enzyme
called DNA recombinase randomly excises most of these segments out of the gene, and splices one V segment to one J
segment. During RNA processing, all but one V and J segment are spliced out. Recombination and splicing may result in
over 10 6possible VJ combinations. As a result, each differentiated B cell in the human body typically has a unique variable
chain. The constant domain, which does not bind antibody, is the same for all antibodies.
1234 Chapter 42 | The Immune System
This OpenStax book is available for free at http://cnx.org/content/col11448/1.10 Figure 42.22 (a) As a germ-line B cell matures, an enzyme called DNA recombinase randomly excises V and J
segments from the light chain gene. Splicing at the mRNA level results in further gene rearrangement. As a result, (b)
each antibody has a unique variable region capable of binding a different antigen.
Similar to TCRs and BCRs, antibody diversity is produced by the mutation and recombination of approximately 300
different gene segments encoding the light and heavy chain variable domains in precursor cells that are destined to become