The term respiration has a broad
• Internal respiration refers to the metabolic
processes occurring in the mitochondria.
Molecular oxygen is used by tissue cells.
Carbon dioxide is produced.
• The respiratory quotient is the carbon dioxide
produced divided by the molecular oxygen
• External respiration is the entire sequence of
events involved in the exchange of oxygen
and carbon dioxide between the external
environment and cells of the body.
• External respiration includes breathing. By
this air is moved between the atmosphere and
alveoli. In addition, oxygen and carbon
dioxide are exchanged between the air in the
alveoli and blood of the pulmonary capillaries.
• Also, oxygen and carbon dioxide are
transported by the blood flowing from the
lungs to the tissues. These gases are
exchanged between the blood and the tissues
The respiratory system carries
out nonrespiratory functions.
• It provides a route for water loss and heat elimination.
• It enhances venous return.
• It contributes to the maintenance of normal acid-base
• It enables various kinds of vocalizations.
• It defends against inhaled foreign matter.
• It modifies, activates, and inactivates materials
passing through the circulatory system.
Respiratory airways conduct air
between the atmosphere and alveoli.
• The walls of the trachea and bronchi are
reinforced with rings of cartilage. This
cartilage is absent in the bronchioles.
• The bronchioles are smooth muscle
tubes, capable of changing the airflow
through them by dilating and constricting.
• Below the trachea, the respiratory tract is
contained in the lungs on the right and left
side of the body. The tract at this point
resembles an inverted tree. It forms
progressively smaller and more numerous
airways (bronchi to bronchioles to alveoli).
• Inhaled air passes through the following series of continuous airways in this
sequence: nasal passages, pharynx, larynx, trachea, bronchi (left and right),
bronchioles, and alveoli.
• The larynx (voice box) has vocal folds. At the base of the trachea, this respiratory
tract spits into a right and left bronchus.
The alveoli are thin-walled,
• Gas exchange is their function.
They are encircled by pulmonary
• The alveoli are close to the
capillaries, offering tremendous
surface area for gas exchange by
• They are a single layer of flattened
Type I alveolar cells.
• Type II alveolar cells secretes
pulmonary surfactant. This
substance facilitates lung
The lungs occupy much of the
• Each has several lobes. Lung tissue is
highly branched airways, alveoli,
pulmonary blood vessels, and large
amounts of elastic connective tissue.
• The heart and several other structures
are between the lungs.
• The outer wall of the chest cavity
consists of 12 pairs of curved ribs. They
join the sternum and thoracic vertebrae.
• The diaphragm separates the thoracic
cavity from the abdominal cavity. The
diaphragm is a skeletal muscle for
• A pleural sac separates each lung from
the thoracic wall. The pleural cavity is
the inside of the pleural sac. Pleural
There are several pressures
inside and outside the lungs.
• Atmospheric pressure is produced by the weight of the air on objects on the surface
of the Earth. It is 760 mm of Hg at sea level and decreases with increasing altitude
above sea level.
• Intra-alveolar (intrapulmonary) pressure is the pressure in the alveoli.
• Intrapleural pressure is in the intrapleural cavity. It averages 756 mm Hg at rest.
This is also written as minus 4, as it is four units below 760 in the atmosphere. It
has a slight vacuum compared to normal atmospheric pressure.
• This is lost during pneumothorax.
• The lungs are normally stretched, filling the large thorax. This is due, in part, to the
intrapleural fluid’s cohesiveness. This stickiness pulls the lungs outward.
• Also, a transmural pressure pushes the lungs outward. This is produced by an
intra-alveolar pressure that is greater than the pressure outside the alveoli.
– See Figures 13-6 and 13-8
Changes in the intra-alveolar
pressure produces the flow of air
into and out of the lungs.
• If this pressure is less than
atmospheric pressure, air
enters the lungs. If the
opposite occurs, air exits from
• Boyle’s law states an inverse
relationship between the
pressure exerted by a quantity
of gas and its volume.
Inspiration begins with the contraction of the
respiratory muscles: the diaphragm (innervated
by the phrenic nerve) and the external
intercostal muscles (innervated by intercostal
• 75 % of the enlargement of the
thoracic cavity during quiet
respiration is due to the contraction
and flattening of the diaphragm.
• This expansion decreases the
intrapleural pressure (down to 754).
The lungs are drawn into this area
of lower pressure. They expand.
This increase in volume lowers the
intra-alveolar pressure to a level
below atmospheric pressure. By
this difference, air enters the lungs.
• The action of accessory inspiratory
muscles can further enlarge the
The onset of expiration begins with the
relaxation of the inspiratory muscles.
• Relaxation of the diaphragm and the muscles of the chest wall,
plus the elastic recoil of the alveoli, decrease the size of the
• The intrapleural pressure increases and the lungs are
• The intra-alveolar pressure increases. When it increases to a
level above atmospheric pressure, air is driven out - an
• Forced expiration can occur by the contraction of expiratory
• These skeletal muscles are ones in the abdominal wall and the
internal intercostal muscles. Their contraction further increases
the pressure gradient between the alveoli (greater pressure) and
– See Figure 13-12
Airway resistance in the respiratory tract
influences the rate of airflow.
• F = delta P
• As the difference between the atmospheric and intra-alveolar pressures
(delta P) is greater, the air flow is greater. This relationship is a direct
• However, if the resistance (R) increases, the airflow is decreased
• The major determinant of resistance is the radius of the conducting
airways. The autonomic nervous system controls the contraction of
the smooth muscle in the walls of the bronchioles, changing their radii.
• Sympathetic stimulation and epinephrine cause bronchodilation.
• Airway resistance is increased abnormally with chronic obstructive
pulmonary disease. Expiration is more difficult than inspiration.
Chronic bronchitis is the long-term inflammatory condition of the
• Asthma is the obstruction of the airways due to inflammation.
Emphysema is the collapse of the alveoli.
The lungs have elastic behavior.
• The lungs have elastic recoil, rebounding if they are stretched.
• Compliance is the effort required to stretch or distend the lungs.
A thin, toy balloon is more compliant than a thick, rubber
• A highly-compliant lung stretches further for a given increase in
pressure than a lung with less compliance.
• Numerous factors decrease lung compliance.
• Pulmonary elastic behavior depends on the pulmonary elastic
behavior and alveolar surface tension. This tension is
determined by the thin liquid film that lines the outside of each
• This film allows the alveolus to resist expansion. This film also
squeezes the alveolus, producing recoil.
• A coating of pulmonary surfactant prevents the alveoli from
collapsing from this surface tension.
• An insufficient amount of pulmonary surfactant can produce
newborn respiratory distress syndrome.
The work of breathing normally
requires 3% of total energy
• Factors such as a decrease of
pulmonary compliance and an
increase in airway resistance
can increase this percentage.
• During each quiet breathing
cycle, about 500 ml of air is
inspired and expired. The
lungs do not completely empty
about each expiration.
Lung volumes and capacities can be
measured by a spirometer. These
• tidal volume (TV) - The air entering or
leaving the lungs in a single breath.
• inspiratory reserve volume - The extra
air that can be maximally inspired over
the typical resting TV.
• inspiratory capacity - The maximum
volume of air that can be inspired at
the end of a normal quiet expiration.
• expiratory reserve volume - The extra volume of air that can be actively expired by
maximal contraction beyond the normal volume of air after a tidal volume.
• vital capacity - The maximum volume of air that can be expired following a maximal
• Various respiratory dysfunctions can be detected by abnormal patterns measured
with the spirometer. Abnormal results include obstructive lung disease and
restrictive lung disease.
Pulmonary ventilation is the
tidal volume x respiratory rate.
• Alveolar ventilation is less because of the anatomic dead space.
These are the airways where air is not available for gas
• Due to this dead space:
• alveolar ventilation =
• (tidal volume - dead space volume) x respiratory rate
• Breathing patterns (e.g., deep and slow) can affect alveolar
• An alveolar dead space also exists, but it is usually small.
• There are local controls on the smooth muscle of the airways.
An accumulation of carbon dioxide in the alveoli decreases
• An increase of oxygen in the alveoli causes pulmonary
vasodilation. It causes vasoconstriction of pulmonary arterioles
Gas exchange occurs by partial pressure gradients.
• The exchange of oxygen and carbon dioxide as
the pulmonary and tissue capillaries is by simple
• Air is a mixture of gases. The partial pressure of
each gas depends on its percentage in the total
atmospheric pressure. For example, nitrogen is
79% of the air. Its partial pressure is 0.79 x 760 =
• A partial pressure gradient is established when
there are two partial pressures for a gas in
different regions of the body.
• For example the partial pressure of oxygen is
greater in the alveoli (e.g., 100) compared to its
partial pressure in the blood of the pulmonary
capillaries (e.g., 40). By this gradient, oxygen
diffuses from the alveoli into these capillaries (100
to 40, higher to lower.
• The partial pressure of carbon dioxide is greater
in the blood of the pulmonary capillaries (e.g., 46)
compared to its partial pressure in the alveoli
(e.g., 40). This gas diffuses into the alveoli.
Partial pressure gradients change the
partial pressures of oxygen(e.g., 100)
and carbon dioxide (e.g., 40) in the
blood returning to the heart from the
• By diffusion, the partial pressures for oxygen and carbon dioxide
in the pulmonary capillaries equilibrate with the partial pressures
for these gases in the alveoli.
• The greater the partial pressure gradients between the alveoli
and the blood, the greater the rate of transfer for the gases.
• The blood passing through the lungs gains oxygen and
eliminates some of its carbon dioxide.
• This blood passes through the left side of the heart and enters
the systemic circulation. It arrives at the tissues with the same
gas content (e.g., 100 for oxygen and 40 for carbon dioxide)
established at lung equilibration.
Other factors in addition to the partial
pressure gradient affect the rate of
• As surface area increases the rate increases. The
alveoli collectively offer a tremendous surface area.
Increased pulmonary blood pressure, from an
increased cardiac output, increases the area.
• The walls of the alveoli and pulmonary capillaries are
thin for rapid gas transfer. Pulmonary edema,
pulmonary fibrosis, and pneumonia thicken the
barriers for gas exchange.
• Gas exchange is also directly proportional to the
diffusion coefficient for a gas. This coefficient is
twenty times as great for carbon dioxide compared to
oxygen, as carbon dioxide is more soluble.
Gas exchange across systemic
capillaries also occurs down
partial pressure gradients.
• By equilibration in the alveoli, the oxygen in the systemic
capillaries has a high partial pressure (e.g., 100) compared to
tissue cells (e.g., 40). These cells are using oxygen.
• The partial pressure for carbon dioxide in the systemic
capillaries is low (e.g., 40) compared to the tissue cells (e.g.,
46), which are making this gas through their metabolism.
• By partial pressure gradients, oxygen diffuses from the systemic
capillaries into the tissue cells (100 to 40, higher to lower).
Carbon dioxide diffuses in the opposite direction.
• Having equilibrated with the tissue cells, the blood leaving the
systemic capillaries is low in oxygen and high in carbon dioxide.
• This blood returns to the right side of the heart and on to the
lungs. At the pulmonary capillaries, the blood acquires oxygen
and releases some of its carbon dioxide.
Most oxygen in the blood is
transported by binding with
• Hemoglobin combines with oxygen to form
oxyhemoglobin. This is a reversible process, favored
to form oxyhemoglobin in the lungs.
• Hemoglobin tends to combine with oxygen as oxygen
diffuses from the alveoli into the pulmonary
• A small percentage of oxygen is dissolved in the
• The dissociation of oxyhemoglobin into hemoglobin
and free molecules of oxygen occurs at the tissue
cells. The reaction is favored in this direction as
oxygen leaves the systemic capillaries and enters
The partial pressure of oxygen is the
main factor determining the percent
• The percent saturation is high where the
partial pressure of oxygen is high (lungs).
• The percent saturation is low where the
partial pressure of oxygen is low (tissue
cells). At the tissue cells oxygen tends to
dissociate from hemoglobin, the opposite
• This relationship is shown in the oxygen-
hemoglobin dissociation curve.
• The plateau part of the curve is where
the partial pressure of oxygen is high
• The steep part of the curve exists at the
systemic capillaries, where hemoglobin
Hemoglobin promotes the net transfer of
oxygen at both the alveolar and tissue
• There is a net diffusion of oxygen from the alveoli to the blood. This
occurs continuously until hemoglobin is as saturated as possible
(97.5% at 100 mm of Hg).
• At the tissue cells hemoglobin rapidly delivers oxygen into the blood
plasma and on to the tissue cells. Various factors promote this
• An increase in carbon dioxide from the tissue cells into the systemic
capillaries increased hemoglobin dissociation from oxygen (shifts the
dissociation curve to the right).
• Increased acidity has the same effect.
• This shift of the curve to the right (more dissociation) is called the Bohr
• Higher temperatures also produces this shift, as does the production of
• Hemoglobin has more affinity for carbon monoxide compared to
Most carbon dioxide (about 60%) is
transported as the bicarbonate ion.
• Carbon dioxide combines with water to form carbonic acid. The
enzyme carbonic anhydrase facilitates this in the erythrocyte.
Carbonic acid dissociates into hydrogen ions and the
• This two-step, reversible process is favored at the tissue cells.
The reverse of this process (bicarbonate ions forming free
molecules of carbon dioxide) occurs in the lungs.
• 30% of the carbon dioxide is bound to hemoglobin in the blood.
This is another means of transport.
• About 10% of the transported carbon dioxide is dissolved in the
• By the chloride shift, the plasma membrane of the erythrocyte
passively facilitates the diffusion of bicarbonate ions (out of the
red cell) and chloride ions.
• By the Haldane effect the removal of oxygen from hemoglobin at
the tissue cells increases the ability of hemoglobin to bind with
Various respiratory states are
characterized by abnormal blood gas
•There are four general categories of hypoxias.
•Examples include hypoxic hypoxia, which is characterized
by a low partial pressure in the arterial blood. In anemia
hypoxia there is reduced oxygen-carrying capacity in the
•Hyperoxia is an above-normal arterial partial pressure of
•Hypercapnia is an excess of carbon dioxide in the blood
caused by hypoventilation.
•Hypocapnia is a below-normal arterial level of carbon dioxide
in the blood, due to hyperventilation.
•Hyperpnea is an increased need for oxygen delivery and
carbon dioxide elimination during exercise.
Respiration is controlled.
• There are respiratory centers in the brain stem
that establish a rhythmic breathing pattern.
• There are inspiratory and expiratory neurons in
the medullary respiratory center.
• The inspiratory neurons send signals to the
inspiratory muscles. When they do not fire
signals, the expiratory center takes over and
• The pneumotaxic center in the pons sends
impulses that switch off the inspiratory neurons.
• The apneustic center in the pons prevents the
inspiratory neurons from being switched off.
• By the Hering-Breuer reflex, stretch receptors
in the lungs are activated when the lungs inflate
with air from an inspiration.
• Signals travel from these receptors to the lungs
by afferent neurons, inhibiting the inspiratory
center. The expiratory center then dominates,
allowing expiration to occur.
• With the completion of this, the inspiratory
center dominates again, starting another
The magnitude of ventilation is
adjusted in response to three
• Peripheral and central chemoreceptors detect
chemical changes in the blood and signal the
medulla to change respiratory rate.
• Respiratory rate increases by:
• either a decrease in the partial pressure of
arterial oxygen or an increase in the partial
pressure of arterial carbon dioxide.
• An increase in hydrogen ions in the blood
also increases this rate. Carbon dioxide-
generated hydrogen ions in the brain are
normally the primary regulators of ventilation.
• These responses keep the partial pressure of
oxygen and carbon dioxide remarkably
• A very low partial pressure of oxygen in the
blood depresses the respiratory center.
Other factors on the control of
respiratory rate include:
• Adjustments in ventilation in response to changes in the arterial
concentration of hydrogen ions are important in acid-base
• A build-up of hydrogen in the blood increases respiratory rate.
The rate of carbon dioxide escape from the lungs increases.
This “pulls” this equation from left to right.
• Hydrogen ions (left) plus water produce carbonic acid. This acid
forms carbon dioxide and water (to the right).
• As a result, hydrogens are removed from the blood as needed,
making adjustment needed to control blood pH.
• Exercise significantly increases ventilation, but the mechanisms
are not clear. Factors such as increased body temperature and
epinephrine release may contribute.
• Ventilation can be influenced by factors unrelated to gas
exchange such as protective reflexes and pain.
During apnea there is a
transient interruption of
– In respiratory arrest it does not continue.
• During dyspnea there is “shortness of
– It often accompanies other conditions such
as pulmonary edema with congestive heart