Selected Lecture Notes

Chapter 22: The Respiratory System (Part 1)

I. The Respiratory System

A. The major function of the respiratory system is respiration.
1. Along with the cardiovascular system, the respiratory system
supplies the body with O2 for cellular respiration and disposes of
CO2, a waste product of cellular respiration.
2. The respiratory system also functions in olfaction and speech.
B. The four processes of respiration involve both the respiratory and
circulatory systems.

Pulmonary ventilation (breathing)-

movement of air into and out Respiratory
of lungs System
External respiration-O2 and CO2
exchange between lungs and blood
Transport-O2 and CO2 in blood
Circulatory
Internal respiration-O2 and CO2 System exchange
between systemic blood
vessels and tissues

The major function of the respiratory system is to supply the body with
oxygen and dispose of carbon dioxide. To accomplish this function, at least
four processes, collectively called respiration, must happen:
1. PULMONARY VENTILATION (commonly called breathing): Air is
moved into and out of the lungs (during inspiration and expiration) so
the gases there are continuously changed and refreshed.
2. EXTERNAL RESPIRATION: Oxygen diffuses from the lungs to the
blood, and carbon dioxide diffuses from the blood to the lungs.
 3. TRANSPORT OF RESPIRATORY GASES: Oxygen is transported from
the lungs to the tissue cells of the body, and carbon dioxide is
transported from the tissue cells to the lungs. The cardiovascular
system accomplishes this transport using blood as the transporting
fluid.
4. INTERNAL RESPIRATION: Oxygen diffuses from blood to tissue cells,
and carbon dioxide diffuses from tissue cells to blood.

Nose
Nasal cavity
Paranasal sinuses
Pharynx
Larynx
Trachea
Bronchi and their smaller branches
Lungs
Alveoli

II. Functional Anatomy of the Respiratory System

A. The respiratory system includes the nose, nasal cavity, and paranasal
sinuses; pharynx, larynx, trachea, and bronchi and their branches; and the
lungs, which contain tiny air sacs, the alveoli.
1. Functionally, the system has two zones:
a. the respiratory zone, composed of the respiratory bronchioles,
alveolar ducts, and alveoli, is the site of gas exchange
b. the conducting zone consists of all other respiratory passageways;
is composed of structures that are conduits to gas exchange sites
c. the diaphragm and other respiratory muscles promote ventilation
(breathing)

B. The Nose and Paranasal Sinuses

Nose:
(1) provides an airway for respiration
(2) moistens and warms entering air
(3) filters and cleans inspired air
(4) serves as a resonating chamber for speech
(5) houses the olfactory (smell) receptors.

1. The nose provides an airway for respiration; moistens, warms, filters,

and cleans incoming air; provides a resonance chamber for speech;
and houses olfactory receptors.
2. The nose is divided into two divisions: the external nose, which is
formed by hyaline cartilage and bones of the skull; and the nasal
cavity, which is entirely within the skull. a. The external nose includes
the root between the eyebrows, bridge and dorsum nasi anteriorly,
ending at the apex, or tip: two exterior openings exist, the external
nares.
b. The nasal cavity is posterior to the external nose and is divided along
the midline by a nasal septum (septal cartilages anteriorly and vomer
and perpendicular plate of ethmoid bone posteriorly), which ends at the
nasopharynx (the part of your throat behind your nose).
EXTERNAL NOSE:

Differences in nasal cartilages = different size and shapes

Skin is thin and contains sebaceous glands
External nose:
Root: between the eyebrows
apex: tip of the nose
nostrils: external openings
Alae: bound nostrils

Nasal cavity: posterior to external nose

septum: divides nasal cavity
roof of nasal cavity: ethmoid and sphenoid bones of the skull
floor formed by the palate:

nasal vestibule: superior to the nostrils, lined with skin n containing

sebaceous and sweat glands and numerous hair follicles
vibrissae: the hair that filter coarse particles (dust, pollen) from inspired air

c. The nasal cavity is lined with two types of mucous membranes: the
olfactory mucosa, containing receptors for smell receptors in
its olfactory epithelium; and the respiratory mucosa, a
pseudostratified columnar epithelium with scattered goblet cells for
mucus production. Goblet cells, that rests on a lamina propria richly supplied
with seromucous nasal glands.
Nasal mucosa: richly supplies with nerve endings, contact with irritable
particles triggers a sneeze reflex
IN action:
Seromucous nasal glands contain mucus-secreting mucous cells with:
lysozyme, an antibacterial enzyme
The epithelial cells of the respiratory mucosa also secrete defensins,
natural antibiotics that help kill invading microbes.

d. Nasal conchae (superior, middle, and inferior) protrude into the nasal
cavity from each lateral wall, increasing the mucosal surface exposure
to air; enhance air turbulence.
Nasal conchae:
scroll-like mucosa-covered projections
they increase the mucosal surface area exposed to air
 enhance air turbulence
e. The nasal cavity is surrounded by paranasal sinuses within the frontal,
maxillary, sphenoid, and ethmoid bones that serve to lighten the skull,
warm and moisten air, and produce mucus. The mucus they produce
ultimately flows into the nasal cavity, and the suctioning effect created by nose
blowing helps drain the sinuses.
The internal nasal cavity lies in and posterior to the external nose

C. The Pharynx
1. The pharynx connects the nasal cavity and mouth superiorly to the
larynx and esophagus inferiorly. It is composed of skeletal muscle and
runs from the base of the skull to C6.
pharynx = throat
5 inches, 13 cm
wall is skeletal muscle
 divided in 3 regions:

Nasopharynx
Oropharynx
Laryngopharynx
a. The nasopharynx serves as only an air passageway and contains the
pharyngeal tonsil (adenoids), which traps and destroys airborne
pathogens. It is lined with pseudostratified columnar epithelium -
pseudostratified ciliated epithelium takes over the job of propelling mucus where
The soft palate and uvula close the
the nasal mucosa leaves off.
nasopharynx during swallowing so that food and liquid do not move up
into the nasal cavity. The pharyngotympanic (auditory) tubes drain into
the nasopharynx and equalize pressure in the middle ear.

b. The oropharynx is an air and food passageway that extends inferiorly

from the level of the soft palate to the epiglottis and houses the
palatine and lingual tonsils.
It is lined with stratified squamous epithelium. This structural adaptation
accommodates the increased friction and chemical trauma (characteristic of hot and spicy
foods) accompanying food passage.

c. The laryngopharynx is an air and food passageway that lies directly

posterior to the epiglottis, extends to the larynx, and is continuous
inferiorly with the esophagus. It is lined with stratified squamous
epithelium.

D. The Larynx
1. The larynx attaches superiorly to the hyoid bone, opening into the
laryngopharynx, and attaches inferiorly to the trachea.
2. The larynx provides an open (patent) airway, routes food and air into the
proper passageways, and produces sound through the vocal cords.
3. The larynx consists of hyaline cartilages: thyroid with laryngeal
prominence (“Adam’s apple”), cricoid, paired arytenoid, paired
corniculate, and paired cuneiform; and the epiglottis, which is elastic
cartilage.
a. The epiglottis is designed to close off the larynx during swallowing to
prevent food or liquids from entering the airways.
b. The larynx houses vocal ligaments that form the true vocal cords
(vocal folds), which vibrate as air passes over them to produce sound.
c. The vocal folds and the medial space between them are called the
glottis.
d. The false vocal cords (vestibular folds) are superior to the vocal folds
and play no part in sound production. They help to close the glottis
during swallowing.
Larynx = voice box (it holds the vocal chords)
2 inches
attaches to the hyoid bone and opens into laryngopharynx
continuous with trachea

Functions:
Provide a patent (open) airway
Act as a switching mechanism to route air and food into the proper
channels
Voice production [because it houses the vocal folds (vocal cords)]

cartilages connecte dy ligaments and membranes

All hyaline cartilages except for epiglottis (elastic cartilage)

- Thyroid cartligae
-Laryngeal prominence - adam's apple
-cricoid cartilage below thryroid
-arytenoid
-cuneiform
-corniculate cartilages
These 3 anchor vocal chords
 Epiglottis

Vocal folds: true vocal chords- vocal ligaments - elastic fibers - lack
blood vessels
vibrate as air rushes up and down the lungs

Glottis: All hyaline cartilages except for epiglottis

false vocal cords - vestibular folds - no direct part in sound production

but help to close the glottis when we swallow.
4. Voice production involves the intermittent release of expired air and the
opening and closing of the glottis.
a. As length and tension of the vocal folds changes, pitch of the voice
varies; generally, as tension increases, pitch becomes higher.
b. Loudness of the voice is determined by the force of the air forced
over the vocal folds.
5. The larynx can act as a sphincter preventing air passage; Valsalva’s
maneuver is a behavior in which the glottis closes to prevent exhalation
and the abdominal muscles contract, causing intra-abdominal pressure to
rise. The Valsalva maneuver helps to empty the rectum or stabilize the
trunk during heavy lifting.

E. The trachea, or windpipe, descends from the larynx through the neck into
the mediastinum, where it terminates at the primary bronchi.
1. The tracheal wall is similar to other tubular body structures, consisting of
a mucosa, submucosa, and adventitia.
2. The trachea is lined with ciliated pseudostratified epithelium, designed
to propel mucus upward toward the pharynx.
3. C-shaped cartilaginous rings associated with the connective tissue
submucosa support the trachea, preventing collapse, while allowing the
esophagus to expand normally during swallowing.
4. The trachealis is smooth muscle that decreases the trachea’s diameter
during contraction, increasing the force of air out of the lungs.
 Trachea: windpipe
Neck to mediastinum
Ends dividing in two main bronchi (primary bronchi)
very flexbe and mobile

trachea wall: layers: mucosa, submucosa, adventitia, hyaline cartilage

Mucosa: pseudostratified epithelium: Its cilia continually propel debris-

laden mucus toward the pharynx

Submucosa: seromucous glands that help produce the mucus “sheets”

within the trachea

16 to 20 C-shaped rings of hyaline cartilage encased by the adventitia

elastic elements make it flexible enough to stretch and move inferiorly

during inspiration and recoil during expiration, but the cartilage rings
prevent it from collapsing and keep the airway patent despite the pressure
changes that occur during breathing.

F. The Bronchi and Subdivisions

Respiratory Zone Structures:

Respiratory zone begin as terminal bronchioles feed into bronchioles in

the lung
From these bronchioles - alveoli

Respiratory bronchioles -> alveolar ducts -> alveolar sacs

Helpful hint: alveolar sac is brunch of grapes, alveoli = individual grape

 1. The conducting zone consists of right and left primary bronchi that enter
each lung and diverge into secondary bronchi that serve each lobe of
the lungs.
2. Secondary bronchi branch into several orders of tertiary bronchi, which
ultimately branch into bronchioles. Bronchioles are less than 1 mm in
diameter; terminal bronchioles can be less than 0.5 mm in diameter.
3. As the conducting airways become smaller, structural changes
occur:
a. The supportive cartilage changes in character until it is no longer
present in the bronchioles. In the bronchioles, elastic fibers replace
cartilage.
b. The mucosal epithelium transitions from pseudostratified columnar, to
columnar, and finally, to cuboidal in the terminal bronchioles.
c. The relative amount of smooth muscle in the walls increases, allowing
significant changes in resistance (either constriction or dilation) to
airflow in the smaller airways.
4. The respiratory zone begins as the terminal bronchioles feed into
respiratory bronchioles that terminate in alveolar ducts within
clusters of alveolar sacs, which consist of alveoli.
a. The respiratory membrane consists of a single layer of squamous
epithelium, type I alveolar cells, surrounded by a basal lamina.
b. The external surface of the alveoli are densely covered by a web of
pulmonary capillaries; the capillary endothelium and the alveolar
epithelium together form the respiratory membrane, across which
gas exchange occurs by simple diffusion.
c. Interspersed among the type I alveolar cells are cuboidal type II
alveolar cells that secrete surfactant. that coats the gas-exposed alveolar
surfaces
d. Alveoli
are surrounded by elastic fibers, contain open alveolar pores,
and have alveolar macrophages.

G. The Lungs and Pleurae

1. The lungs occupy all of the thoracic cavity except for the mediastinum;
each lung is suspended within its own pleural cavity and connected to the
mediastinum by vascular and bronchial attachments called the lung root.
2. The left lung is smaller than the right because the position of the heart
shifts the left lung slightly to the left; each lung is divided into lobes,
separated from each other by fissures.
3. Each lobe contains a number of bronchopulmonary segments, each
served by its own artery, vein, and tertiary bronchus. They are separated
by connective tissue septa, and if diseased, can be individually removed.
4. Lung tissue consists largely of air spaces, with the balance of lung tissue
comprised mostly of elastic connective tissue.
Lungs occupy the thoracic cavity except the mediastinum.

curving costal surface in contact with rib

Apex - close to clavicle

Base - rests on diaphragm
hilum- indentation though which other structures enter and leave the lung

Left lung is smaller

Left lung: divdied into superior and inferior lobes by oblique fissure

right lung: partitioned into superior, middle, and inferior lobes by the
oblique and horizontal fissures.

Each lobe has pyramid shaped bronchopulmonary segments separated r

by connective tissue septa. The right lung has 10 bronchopulmonary
segments, but the left lung 8 - 10.

lobules: hexagons seen at naked eye, subdivisions of lungs

lungs consist largely of air space

stroma = balance of lung tissue = elastic connective tissue
 lungs are soft, spongy, elastic organs

5. There are two circulations that serve the lungs:

a. The pulmonary network carries systemic blood to the lungs for
oxygenation; the pulmonary veins carry oxygenated blood from the
respiratory zones to the left atrium of the heart.
Pulmonary arteries: deliver oxygenated blood to lungs
They branche profusely along with the bronchi and finally feed into the
pulmonary capillary networks surrounding the alveoli

Pulmonary veins: convey oxygenated blood from repsiratory zone to

the heart - Left atrium.
Their tributaries course back to the hilum both with the corresponding
bronchi and in the connective tissue septa separating the
bronchopulmonary segments.
Pulmonary circuit: low pressure, high volume

b. The bronchial arteries provide systemic blood to the lung tissue. They
arise from the aorta. Enter lungs at hilum and run along bronchi.
High ressure, low volume

6. The lung capillary endothelium contains enzymes that act on substances

in the blood, i.e.
angiotensin-converting enzyme activates blood pressure hormone.
7. The lungs are innervated by parasympathetic and sympathetic motor
fibers that constrict or dilate the airways, as well as visceral sensory
fibers.
Parasympathetic fibers: constrict air tubes
Sympathetic fibers dilate

8. The pleurae form a thin, double-layered serosa.

a. The parietal pleura covers the thoracic wall, superior face of the
diaphragm, and continues around the heart between the lungs.
 b. The visceral pleura covers the external lung surface, following its
contours and fissures.
c. Pleural fluid lubricates the space between the pleurae (pleural cavity)
to allow friction-free movement during breathing.
d. The pleurae help divide the thoracic cavity into three discrete
chambers, preventing one organ’s movement (example lung and heart)
from interfering with another’s, as well as limiting the spread of
infection.

III. Mechanics of Breathing

Breathing = pulmonary ventilation: 2 phases: inspiration and expiration

Respiratory pressures ARE always relative to atmospheric pressure Patm

which is the pressure exerted by the air (gases) surrounding the body.

At sea level, atmospheric pressure is 760 mm Hg = 1 atm

A. Respiratory pressures are described relative to atmospheric pressures:
a (-) negative pressure indicates that the respiratory pressure is lower
than atmospheric pressure, while a (+) positive pressure indicates that
the respiratory pressure exceeds atmospheric pressure. (0) Zero
respiratory pressure means that respiratory pressure is equal to
atmospheric pressure.
1. Intrapulmonary pressure (P pul) is the pressure in the alveoli, which
rises and falls during respiration, but always eventually equalizes with
atmospheric pressure.
2. Intrapleural pressure (P ip) is the pressure in the pleural cavity. It also
rises and falls during respiration, but is always about 4 mm Hg less
than intrapulmonary pressure. That is, P is always negative relative to P .
ip pul

a. The negative intrapleural pressure is due to the opposition of two

forces:
recoil force and surface tension of alveolar fluid in the lungs vs. the
natural tendency of the chest wall to pull outward (by the natural elasticity
of the chest wall, a force that tends to pull the thorax outward and enlarge the
lungs.)
 FORCES IN THE THORAX:
There are opposite forces
Two forces act to pull the lungs (visceral pleura) away from the thorax
wall (parietal pleura) and cause the lungs to collapse:

THE LUNGS’ NATURAL TENDENCY TO RECOIL. Because of

their elasticity, lungs always assume the smallest size possible.
THE SURFACE TENSION OF THE ALVEOLAR FLUID. The molecules of the fluid
lining the alveoli attract each other. This produces surface tension that constantly
acts to draw the alveoli to their smallest possible dimension.

b. Neither force overcomes the other due to the fluid adhesion between
the pleural membranes created by the presence of pleural fluid.
3. Atmospheric pressure, the pressure exerted by air surrounding the body,
is equal to 760 mm Hg at sea level = 1 atmosphere.

Transpulmonary Pressure
The transpulmonary pressure is the difference between the intrapulmonary and
intrapleural pressures (P – P ). It is thispressure that keeps the air spaces of the lungs
pul ip

open or, phrased another way, keeps the lungs from collapsing. Moreover, the size of the
transpulmonary pressure determines the size of the lungs at any time—the greater the
transpulmonary pressure, the larger the lungs. We cannot overemphasize the
importance of negative pressure in the intrapleural space and the tight coupling of the
lungs to the thorax wall. Any condition that equalizes P with the intrapulmonary (or
ip

atmospheric) pressure causes immediate lung collapse

B. Pulmonary Ventilation = BREATHING

1. Pulmonary ventilation (inspiration and expiration) is a mechanical
process causing gas flow into and out of the lungs according to volume
changes in the thoracic cavity.

volume changes lead to pressure changes, and pressure changes lead to the flow of
gases to equalize the pressure.
 a. Boyle’s law states that at a constant temperature, the pressure of a
gas varies inversely with its volume. That means, when volume
increases, pressure decreases; when volume decreases, pressure
increases.

P1V1 = P2V2

Volume changes  pressure changes  gases flow from an area of

higher pressure to lower pressure to equalize the pressure

2. During quiet inspiration, the diaphragm and intercostal muscles

contract, resulting in an increase in thoracic volume. The diaphragm
descends while the intercostal muscles lift the rib cage. Both actions
increase the volume of the thoracic cavity, which causes intrapulmonary
pressure to drop below atmospheric pressure (to -1 mm Hg), and air
flows into the lungs.

INSPIRATION:

Air flows from high to low pressure

1- Diaphragm contracts, flattens out and as a result height of thoracic

cavity increases

2- Intercostal muscles contract they lift the rib cage and pull sternun
superiorly

!!!!!= Volume increases by almost 500 ml

!!!!!= P pul drops

Anytime the intrapulmonary pressure is less than the atmospheric

pressure (P pul < P atm), air rushes into the lungs along the pressure
gradient. Inspiration ends when P pul = P atm.
 3. During forced inspiration, accessory muscles of the neck and thorax
contract (scalenes, sternocleidomastoid, pectoralis minor), increasing
thoracic volume beyond the increase in volume during quiet inspiration.
Forced inspiration occurs during vigorous exercise or in patients with
COPD.
4. Quiet expiration is a passive process that relies mostly on elastic recoil
of the lungs as the thoracic muscles relax. Thoracic cavity volume
decreases, leading to an increase in pressure. Intrapulmonary pressure
rises above atmospheric pressure (to +1 mm Hg) and air flows out of the
lungs down its pressure gradient (from an area of higher pressure to
lower pressure). When P > P , the pressure gradient forces gases to flow out of
pul atm

the lungs.
5. Forced expiration is an active process relying on contraction of
abdominal muscles to increase intra-abdominal pressure and depress the
rib cage.

C. Physical Factors Influencing Pulmonary Ventilation

1. Airway resistance is the friction encountered by air in the airways; gas
flow is reduced as airway resistance increases. Friction is the major
nonelastic source of resistance to gas flow. The relationship between
flow (F), pressure (P), and resistance (R) is:

F = ΔP
R
Resistance is mostly determined by diameters of conducting tubes

a. Airway resistance is greatest in the medium-sized airways due to two

factors: upper airways are very large diameter, and lower airways,
while smaller, are very numerous.

At terminal bronchioles, gas flow stops and diffusion takes over as the main force
driving gas movement, so resistance is no longer an issue.
 2. Alveolar surface tension due to water in the alveoli acts to draw the
walls of the alveoli together, presenting a force that must be overcome in
order to expand the lungs.
What makes this possible:
a. Surfactant, produced by type II alveolar cells, reduces
alveolar surface tension to an optimal amount. Surfactant is a
detergent-like lipid and protein complex produced by type II alveolar
cells. It reduces surface tension of the alveolar fluid and discourages
alveolar lung collapse. As a result, the surface tension of alveolar fluid is
reduced, and less energy is needed to overcome those forces to expand the lungs
and discourage alveolar collapse.
An insufficient quantity in premature infants causes infant respiratory
distress syndrome in which the alveoli collapse after each breath.

3. Lung compliance is determined by distensibility of lung tissue and the

surrounding thoracic cage and alveolar surface tension.
a. Any decrease in resilience reduces compliance; factors such as chronic
inflammation, the presence of nonelastic scar tissue, or decreased
surfactant can reduce resilience of the lungs. Decreased flexibility of
the thoracic cage can also diminish lung compliance. The flexibility of
the thoracic cage decreases when costal cartilages ossify or intercostal
muscles become paralyzed.
healthy lungs tend to have high compliance, which favors efficient ventilation.

D. Respiratory Volumes and Pulmonary Function Tests (You will experiment

with these concepts in the laboratory portion of the course.)
1. Respiratory volumes and specific combinations of volumes, called
respiratory capacities, are used to gain information about a person’s
respiratory status.
Spirometer: CLINICAL Measuring tool, patients blow into it
a. Tidal volume (TV) is the amount of air that moves in and out of the
lungs with each breath during quiet breathing and averages 500 ml per
breath.
b. The inspiratory reserve volume (IRV) is the amount of air that can be
forcibly inspired beyond a normal tidal volume inspiration (2100–3200
ml).
c. The expiratory reserve volume (ERV) is the amount of air that can be
evacuated from the lungs after tidal expiration (1000–1200 ml).
d. Residual volume (RV) is the amount of air that remains in the lungs
after maximal forced expiration (about 1200 ml).

Air still remains in there after normal inspiration to keep the alveoli open
and prevent lung collapse.

2. Respiratory capacities are sums of multiple respiratory

volumes.
a. Inspiratory capacity (IC) is the sum of tidal volume and
inspiratory reserve volume and represents the total amount
of air that can be inspired after a tidal expiration.
b. Functional residual capacity (FRC) is the combined
residual volume and expiratory reserve volume and
represents the amount of air that remains in the lungs after
a tidal expiration.
c. Vital capacity (VC) is the sum of tidal volume,
inspiratory reserve, and expiratory reserve volumes and is
the total amount of exchangeable air.
d. Total lung capacity (TLC) is the sum of all lung
volumes.
3. The anatomical dead space is the volume of the conducting zone
conduits, roughly 150 ml, which is a volume that never
contributes to gas exchange in the lungs. This means that if TV is
500 ml, only 350 ml of it is involved in alveolar ventilation.
4. Pulmonary function tests evaluate losses in respiratory function
using a spirometer to distinguish between obstructive and
restrictive pulmonary disorders. Obstructive and restrictive
lung disease share the same main symptom: shortness of breath
with exertion.
 a. Obstructive pulmonary diseases involve hyperinflation of the lungs
and are characterized by increased TLC, FRC, and RV. Obstructive lung
diseases include conditions that make it hard to exhale all the air in the
lungs. At the end of a full exhalation, an abnormally high amount of air
may still linger in the lungs. The most common causes of obstructive
pulmonary disease is asthma, bronchitis, emphysema, and cystic fibrosis.

b. Restrictive pulmonary disorders, in which expansion of the lungs is

limited, display low VC, TLC, FRC, and RV. People with restrictive
lung disease have difficulty fully expanding their lungs with air.
Restrictive lung disease most often results from a condition causing
stiffness in the lungs themselves. In other cases, stiffness of the chest
wall, weak muscles, or damaged nerves may cause the restriction in
lung expansion.

9. What is the driving force for pulmonary ventilation?

The driving force for pulmonary ventilation is a pressure gradient created by changes
in the thoracic volume.
10. What causes the intrapulmonary pressure to decrease during inspiration?
The intrapulmonary pressure decreases during inspiration because of the increase in
thoracic cavity volume brought about by the muscles of inspiration.
11. What causes the partial vacuum (negative pressure) inside the pleural cavity? What
happens to a lung if air enters the pleural cavity? What is the clinical name for this
condition?
The partial vacuum (negative pressure) inside the pleural cavity is caused by the
opposing forces acting on the visceral and parietal pleurae. The visceral pleurae are
pulled inward by the lungs’ natural tendency to recoil and the surface tension of the
alveolar fluid. The parietal pleurae are pulled outward by the elasticity of the chest
wall. If air enters the pleural cavity, the lung on that side will collapse. This
condition is called pneumothorax.
12. Premature infants often lack adequate surfactant. How does this affect their ability to
breathe?
lack of surfactant increases surface tension in the alveoli and causes them to collapse between
breaths. (In other words, it markedly decreases lung compliance
 Selected Lecture Notes

Chapter 22: The Respiratory System (Part 2)

Gas Exchanges between the Blood, Lungs, and Tissues

A. Gases have basic properties, as defined by Dalton’s law of partial
pressures and Henry’s law.
1. Dalton’s law of partial pressures states that the total pressure exerted
by a mixture of gases is the sum of the pressures exerted by each gas in
the mixture. Partial pressure is the pressure exerted by each gas in the
mixture. Partial pressure is directly proportional to the gas’s percentage
in the mixture.
2. Henry’s law states that when a mixture of gases is in contact with a
liquid, each gas will dissolve in the liquid in proportion to its partial
pressure. The amount of gas that dissolves depends on the solubility of
the gas and temperature. CO2 is 20 times more soluble in water than O2;
little N2 dissolves in water. As temperature rises, solubility decreases.

EXTERNAL EXPIRATION:
Oxygen enters and carbon dioxide leaves the blood in the lungs by
diffusion
INTERNAL INSPIRATION:
At the body tissues, the same gases move in opposite directions, also by
diffusion.

The direction and amount of movement of a gas are determined by its

partial pressure in the two phases. This flexible situation is exactly what
occurs when gases are exchanged in the lungs and tissues. For example,
when PCO2 in the pulmonary capillaries is higher than in the lungs, CO2
diffuses out of the blood and enters the air in the alveoli.
B. The composition of alveolar gas differs significantly from atmospheric
gas due to gas exchange occurring in the lungs, humidification of air by
conducting passages, and mixing of alveolar gas that occurs with each
breath. Alveoli contain more CO2 and water vapor than atmospheric air.
What causes these differences:

Gas exchanges occurring in the lungs (O2 diffuses from the alveoli
into the pulmonary blood and CO2 diffuses in the opposite
direction).

Humidification of air by conducting passages.

The mixing of alveolar gas that occurs with each breath. Because
only 500 ml of air enter with each tidal inspiration, gas in the alveoli
is actually a mixture of newly inspired gases and gases remaining in
the respiratory passageways between breaths.

The alveolar partial pressures of O2 and CO2 are easily changed by

increasing breathing depth and rate. A high AVR brings more O2 into
the alveoli, increasing alveolar PO2 and rapidly eliminating CO2 from
the lungs.

C. External Respiration
External respiration: pulmonary gas exchange!
Dark red blood with CO2 -> brighter red (O2 + biding to hemoglobin
1. External respiration involves O2 uptake and CO2 unloading from
hemoglobin in red blood cells. It is the exchange of O2 and CO2 across
the respiratory membrane.
External respiration is influenced by three factors:
 partial pressure gradients and gas solubilities,
 thickness and surface area of the respiratory membrane,
 and ventilation-perfusion coupling.
Factors influencing EXTERNAL respiration:
 Partial pressure gradients and gas solubilities:
• A steep partial pressure gradient exists between blood in the
pulmonary arteries and alveoli, and O2 diffuses rapidly from the
alveoli into the blood, until it reaches equilibrium at PO2 of 104 mm
Hg.
• P O2 of deoxygenated blood in the pulmonary arteries: 40 mm Hg
• PO2 in the alveoli: 104 mm Hg
• Result: O2 diffuses rapidly from the alveoli into pulmonary capillary
blood
• Carbon dioxide moves in the opposite direction along a partial
pressure gradient that is much less steep (45 to 40), reaching equilibrium at
40 mm Hg. Still, equal amounts of CO2 and O2 are exchanged because
CO2 is 20 times more soluble in plasma and alveolar fluid than O2.
• The difference in the degree of the partial pressure gradients of
oxygen and carbon dioxide reflects the fact that carbon dioxide is
much more soluble than oxygen in the blood.

Thickness and surface area of the respiratory membrane

2. The respiratory membrane is normally very thin (0.5 to 1 µm thick)
and presents a huge surface area (40 times that of skin) for efficient gas
exchange. The respiratory membrane thickens if lungs become
waterlogged and edematous. The surface area of the respiratory
membrane declines with emphysema (walls of adjacent alveoli break
down), tumors, inflammation, and mucus.

Ventilation-perfusion coupling (matching alveolar ventilation with

pulmonary blood perfusion)

3. Ventilation-perfusion coupling ensures a close match between the

amount of gas reaching the alveoli and the blood flow in the pulmonary
capillaries.
a. In order to optimize perfusion and maximize oxygen uptake into
the blood, arterioles feeding areas with low PO2 constrict, while
arterioles serving well ventilated areas dilate.
P controls perfusion by changing arteriolar diameter.
O2

P controls ventilation by changing bronchiolar diameter.

CO2

b. To increase ventilation so that there can be more rapid elimination

of CO2 from the body, bronchioles serving areas with high alveolar
CO2 dilate, but in areas with low CO2, bronchioles constrict.
c. Ventilation and perfusion are balanced so that they work together to
make O2 and CO2 levels match physiological demands.

If alveolar ventilation is inadequate, local PO2 is low because blood

takes O2 away more quickly than ventilation can replenish it. As a
result, the terminal arterioles constrict, redirecting blood to respiratory
areas where PO2 is high and oxygen pickup is more efficient.

Bronchioles servicing areas where alveolar CO levels are high dilate, allowing
2

CO to be eliminated from the body more rapidly. Bronchioles serving areas where
2

P is low constrict.
CO2

The changing diameter of local bronchioles and arterioles synchronizes

alveolar ventilation and pulmonary perfusion. Poor alveolar ventilation
results in low oxygen and high carbon dioxide levels in the alveoli.
Consequently, pulmonary arterioles constrict and airways dilate,
 bringing blood flow and air flow into closer physiological match. High
PO2 and low PCO2 in the alveoli cause bronchioles serving the alveoli
to constrict, and promote flushing of blood into the pulmonary
capillaries.

D. Internal Respiration
1. Internal respiration involves capillary gas exchange in body tissues.
2. The diffusion gradients for oxygen and carbon dioxide are reversed from
those for external respiration and pulmonary gas exchange.
3. The partial pressure of oxygen in the tissues is always lower than the
blood, so oxygen diffuses readily into the tissues, while a similar but less
dramatic gradient exists in the reverse direction for carbon dioxide.

• Tissue cells continuously use O2 for their metabolic activities and

produce CO2.
• PO2 is always lower in tissues than it is in systemic arterial blood
(40 mm Hg versus 100 mm Hg)
• O2 moves rapidly from blood into tissues until equilibrium is
reached
• At the same time, CO2 moves quickly along its pressure gradient
into blood.
• As a result, venous blood draining the tissue capillary beds and
returning to the heart has a PO2 of 40 mm Hg and a PCO2 of 45 mm
Hg.
In summary, the gas exchanges that occur between blood and alveoli and
between blood and tissue cells take place by simple diffusion. They are
driven by the partial pressure gradients of O2 and CO2 that exist on the
opposite sides of the exchange membranes.

Transport of Respiratory Gases by Blood

A. Oxygen Transport
Oxygen carried in blood in 2 ways:
1.5% dissolved in plasma
 98.5% bound to hemoglobin
Hb has 4 polypeptide chains, each bound to a Fe contining heme group
Each Fe atom can bind to one Oxygen
.: each hemoglobin molecule can combine with four molecules of O2

1. Because molecular oxygen is poorly soluble in the blood, only 1.5% is

dissolved in plasma, while the remaining 98.5% must be carried on
hemoglobin.
a. Up to four oxygen molecules can be reversibly bound to a molecule
of hemoglobin—one oxygen on each iron.

Lungs
HHb + O2  HbO2 + H+

Tissues

• Oxyhemoglobin (HbO2): hemoglobin – O2 combination

• Deoxyhemoglobin (HHb): hemoglobin that has released
O2; also called reduced hemoglobin

b. Theaffinity of hemoglobin for oxygen changes with each

successive oxygen that is bound or released, making oxygen loading
and unloading very efficient.

The rate at which Hb reversibly binds or releases O2 is regulated by:

PO2, temperature, blood pH, PCO2, and blood concentration of an
organic chemical called BPG. These factors interact to ensure that
adequate O2 is delivered to tissue cells.

2. At higher plasma partial pressures of oxygen, hemoglobin unloads little

oxygen, but if plasma partial pressure falls dramatically, such as during
vigorous exercise, much more oxygen can be unloaded to the tissues.
3. Temperature, blood pH, PCO2, and the amount of BPG in the blood
(produced by RBCs during glycolysis) all influence hemoglobin
saturation at a given partial pressure. Increases in temperature, H+, PCO2,
and BPG
a. Modify the structure of hemoglobin such that it decreases its
affinity for O2
b. Occur in systemic capillaries
c. Enhance O2 unloading from blood
As cells metabolize glucose and use O2,
(Do you remember the equation for cellular respiration?
glucose + oxygen  ATP + water + carbon dioxide + heat)

PCO2 and H+ increase in capillary blood  declining blood pH and

increasing PCO2.
The Bohr effect ensures that the hemoglobin-oxygen bond weakens and
oxygen unloading occurs where it is needed most.

As cells metabolize glucose and use O2 they release CO2

This increases the PCO2 and H+ levels in capillary blood
Both declining blood pH (acidosis) and increasing PCO2 weaken the Hb-
O2 bond, a phenomenon called the Bohr effect. This enhances oxygen
unloading where it is most needed.
B. Carbon Dioxide Transport
1. Carbon dioxide is transported in the blood in three ways:
• 7–10% is dissolved in plasma
• 20% is carried on hemoglobin bound to globin (called
carbaminohemoglobin) CO2+Hb⇌HbCO2carbaminohemoglobi
• 70% exists as bicarbonate ion (HCO3-) in plasma, an important
buffer of blood pH.
CO2 binds to the heme
CO2 dissociates from Hb to lungs where PCO2 in alveoli is lower than in
blood
CO2 binds to Hb in the tissues where PCO2 is higher than in blood
2. The Haldane effect encourages CO2 exchange in the lungs and
tissues: When plasma partial pressure of oxygen and oxygen saturation
of hemoglobin decrease, more CO2 can be carried in the blood.

3. The carbonic acid–bicarbonate buffer system of the blood is formed

when CO2 combines with water and dissociates, producing carbonic acid
and bicarbonate ions that can release or absorb hydrogen ions.

The above reaction occurs primarily in RBCs, where carbonic

anhydrase reversibly and rapidly catalyzes the reaction.
Carbonic anhydrase: enzyme that reversibly facilitates the joining of
carbon dioxide with water to form carbonic acid
It makes the reaction faster

4. In systemic capillaries, HCO3- quickly diffuses from RBCs into the

plasma. The chloride shift then occurs  outrush of HCO3- from RBCs
is balanced as Cl- moves into RBCs from the plasma.

5. The carbonic acid-bicarbonate buffer system resists changes in blood

pH. If the H+ (hydrogen ion) concentration in blood rises, excess H+ is
removed by combining with HCO3 to yield H2CO3. If H+ concentration
begins to drop, H2CO3 dissociates, releasing H+.

CO2 transport
H+ released binds to Hb
triggering the Bohr effect
CO2 loading enhances O2 release

Hb acts as buffer, H+ causes a little change in pH and blood becomes

only slightly more acidic
 H+ released binds to Hb
triggering the Bohr effect
CO2 loading enhances O2 relase
Hb acts as buffer, H+ causes a little change in pH and blood becomes
only slightly more acidic.

HCO3- moves from RBC to plasma where it is carried to lungs

Cl- move from plasma to RBCs ( chloride shift) to counterbalance

In the lungs:
Blood PCO2 declines 45 -> 40
For this to occur:
HCO3- reenters RBCs and binds to H+ => CARBONIC ACID is formed
Cl- moves to plasma

Carbonic anhydrase: splits carbonic acid to release CO2 and water.

CO2 diffuses along its partial pressure gradient from the blood into the
alveoli.

The lower the PO2 and the lower the Hb saturation with oxygen, the
more CO2 that blood can carry. This phenomenon, called the Haldane
effect, reflects the greater ability of reduced hemoglobin to form
carbaminohemoglobin and to buffer H+ by combining with it. As CO2
enters the systemic bloodstream, it causes more oxygen to dissociate
from Hb (Bohr effect). The dissociation of O2 allows more CO2 to
combine with Hb (Haldane effect).
The Haldane effect encourages CO2 exchange in both the tissues and
lungs.

6. Changes in respiratory rate and depth affect blood pH.

a. Slow, shallow breathing  increased CO2 in blood  drop in pH
(more acidic)
 b. Rapid, deep breathing  decreased CO2 in blood  rise in pH
(less acidic)

Control of Respiration
A. Neural Mechanisms
Neural mechanisms involved in the control of respiration:
Medullary Respiratory Centers
Medulla oblongata

The ventral respiratory group (VRG), a network of neurons that

extends in the ventral brain stem from the spinal cord to the pons-medulla
junction

The dorsal respiratory group (DRG), located dorsally near the root of
cranial nerve IX

1. Two areas of the medulla oblongata are critically important to

respiration: the dorsal respiratory group near the root of cranial nerve IX
and the ventral respiratory group extending from the spinal cord to the
pons-medulla junction.

2. The ventral respiratory group (VRG) is a rhythm-generating and

integration center containing separate groups of neurons, some that fire
during inhalation and others that fire during exhalation.

a. The inspiratory neurons, via phrenic and intercostal nerves, stimulate

contraction of the diaphragm and intercostal muscles. => thorax
expands and air rushes into lungs

b. When the expiratory neurons fire, output to the respiratory muscles

stops, muscles relax, and lungs recoil.
 3. The cyclic behavior of inspiratory and expiratory neurons produces a
breathing rate of 12–15 breaths per minute, which is called eupnea. -
normal respiratory rate and rhythm
Severe hypoxia: VRG generates gasping, respiration stops when a certain
luster of VRG neurons is completely suppressed

4. The dorsal respiratory group (DRG) integrates input from peripheral

stretch and chemoreceptors, then sends information to the VRG.
4. The pontine respiratory centers within the pons modifies the breathing
rhythm and prevents overinflation of the lungs through an inhibitory
action on the medullary respiration centers. Happens during certain
activities such as vocalization, sleep, and exercise

5. It is likely that reciprocal inhibition on the part of the different respiratory

centers is responsible for the rhythm of breathing.

B. Factors Influencing Breathing Rate and Depth

Inspiratory depth: determined by how actively the respiratory centers
stimulate the motor neurons serving the respiratory muscles. The greater
the stimulation, the greater the number of motor units excited and the
greater the force of respiratory muscle contractions.

Respiratory rate: determined by how long the inspiratory center is active

or how quickly it is switched off.

The respiratory centers in the medulla and pons are sensitive to both
excitatory and inhibitory stimuli:

1. The most important factors influencing breathing rate and depth are
changing levels of CO2, O2, and H+ in arterial blood. But, rising CO2
levels is the most powerful respiratory stimulant.
a. The receptors monitoring fluctuations in these parameters are the
central chemoreceptors in the medulla oblongata and the
peripheral chemoreceptors in the aortic arch and carotid arteries.
b. Rising CO2 levels in the cerebrospinal fluid result in stimulation of the
central chemoreceptors, and ultimately lead to an increase in rate and
depth of breathing. CO2 is hydrated in the brain  carbonic acid with
dissociates, releasing H+  drop in pH. H+ stimulates the central
chemoreceptors located in the brain stem. The chemoreceptors synapse
with respiratory regulatory centers  leads to an increased depth and
rate of breathing  lowers blood PCO2  pH rises.
c. Again, as H+ accumulates in the plasma, rate and depth of breathing
increase in an attempt to eliminate carbonic acid from the blood
through the loss of CO2 in the lungs.

P CO2 levels rise (hypercapnia)

CO2 accumulates in the brain
CO2 hydrated to form carbonic acid
Acid dissociates, H+ is liberated, and the pH drops.
Increase in H+ excites chemoreceptors
RESULT: depth and rate of breathing increase, alveolar ventilation
enhances, CO2 flushes out of blood - pH rises

PCOs elevation => doubles alveolar ventilation

Notice that while rising blood CO2 levels act as the initial stimulus, it
is rising levels of H+ generated within the brain that prod the central
chemoreceptors into increased activity. (CO2 readily diffuses across
the blood brain barrier between the brain and the blood, but H+ does
not.) In the final analysis, control of breathing during rest is aimed
primarily at regulating the H + concentration in the brain.

d. Peripheral chemoreceptors in the aortic and carotid bodies act as

arterial O2 sensors. Declining PO2 normally has only a slight effect on
 ventilation. Arterial PO2 must drop substantially, to at least 60 mm Hg,
before O2 levels become a major stimulus for increased ventilation.
there is a huge reservoir of O bound to Hb, and Hb remains almost entirely
2

saturated unless or until the P of alveolar gas and arterial blood falls below 60
O2

mm Hg.
Influence of pH: H+ doesn’t cross the blood brain barrier, response to
falling arterial pH levels mediated through peripheral chemoreceptors
As Ph declines, control systems increase respiratory rate and
depth to eliminate CO2 and carbonic acid from the blood.

Influence of higher brain centers:

2. Higher brain centers alter rate and depth of respiration.

a. The limbic system, strong emotions, and pain activate the
hypothalamus, which modifies respiratory rate and depth.
Examples: breath-holding that occurs when we are angry and the increased
respiratory rate that occurs when we are excited. A rise in body temperature
raises the respiratory rate, while a drop in body temperature produces the
opposite effect.
b. Thecerebral cortex can exert voluntary control over respiration by
bypassing the medullary centers and directly stimulating the respiratory
muscles. VOLUNTARY CONTROL – cortical control

3. Pulmonary irritant reflexes respond to inhaled irritants in the nasal

passages or trachea by causing reflexive bronchoconstriction in the
respiratory airways.

4. The inflation, or Hering-Breuer, reflex is activated by stretch receptors

in the visceral pleurae and conducting airways, protecting the lungs
from overexpansion by inhibiting inspiration. More of a protective
function.

Respiratory Adjustments
A. Exercise
 1. During vigorous exercise, deeper and more vigorous respirations, called
hyperpnea, ensure that tissue demands for oxygen are met.
Working muscles consume large amts of O2 and produce large amts of
CO2 => ventilation increases Hyperpnea
Hyperpnea vs. Hyperventilation

Hyperpnea doesn’t alter blood O2 and CO2 levels significantly

Hyperventilation is excessive ventilation, and is characterized by low
PCO2 and alkalosis.

2. Three neural factors contribute to the change in respiration in exercise:

 psychic stimuli
 cortical stimulation of skeletal muscles and respiratory centers,
 excitatory impulses to the respiratory areas from active muscles,
tendons, and joints.

B. High Altitude
1. Acute mountain sickness (AMS) may result from a rapid transition from
sea level to altitudes above 8000 feet. P O2 here is lower
Symptoms: headaches, shortness of breath, nausea, and dizziness.
2. A long-term change from sea level to high altitudes results in
acclimatization of the body, including an increase in ventilation rate,
lower than normal hemoglobin saturation, and increased production of
erythropoietin.
High altitude = lower Hb saturation levels a less O2 is available
Hb affinity for O2 is reduced as BPG concentrations increase
Kidney produce more erythropoietin when O2 level decline

Homeostatic Imbalances of the Respiratory System

A. Chronic obstructive pulmonary diseases (COPD) are seen in patients
that have a history of smoking and result in progressive dyspnea, coughing
and frequent pulmonary infections, and respiratory failure. Major cause of
 disability and death in North America. Irreversible decrease in ability to
force air out of the lungs
1. Obstructive emphysema is characterized by permanently enlarged
alveoli and deterioration of alveolar walls. Lungs loose elasticity. Causes:
smoking, hereditary (alpha-1 antitrypsin deficiency).
2. Chronic bronchitis results in excessive mucus production, as well as
inflammation and fibrosis of the lower respiratory mucosa. Result:
airways are obstructed, lung ventilation is impaired. Infections as bacteria
thrive in mucus. Smoking major risk factor. Pollution

B. Asthma is characterized by coughing, dyspnea, wheezing, and chest

tightness brought on by active inflammation of the airways.
Asthma is marked by acute episodes followed by symptom-free periods—that
is, the obstruction is reversible.

C. Tuberculosis (TB) is an infectious disease caused by the bacterium

Mycobacterium tuberculosis and is spread by coughing and inhalation.
Lungs and can spread to other organs

D. Lung Cancer
1. In both sexes, lung cancer is the most common type of malignancy and is
strongly correlated with smoking.
2. Adenocarcinoma originates in peripheral lung areas as nodules that
develop from bronchial glands and alveolar cells.
3. Squamous cell carcinoma arises in the epithelium of the bronchi and
tends to form masses that hollow out and bleed.
4. Small cell carcinoma contains lymphocyte-like cells that form clusters
within the mediastinum and rapidly metastasize.
5. Victims die one year of diagnosis, preventable.
6. Aggressive, metastasizes rapidly and widely
7. Smoke impair the functioning of cilia
E. Cystic Fibrosis
1. Cystic fibrosis is the most common lethal genetic disease in North
America. It is characterized by abnormal, viscous mucus that clogs
respiratory passageways, leading to bacterial infections. It not only
affects the lungs, but also the pancreatic ducts and reproductive ducts.