The respiratory system
The cells of the body require a continuous supply of oxygen to produce
energy and carry out their metabolic functions. Furthermore, these
aerobic
metabolic processes produce carbon dioxide, which must be continuously
eliminated. The primary functions of the respiratory system include:
• Obtaining oxygen from the external environment and supplying it to the
body’s cells
• Eliminating carbon dioxide produced by cellular metabolism from the
body
The process by which oxygen is taken up by the lungs and carbon dioxide
is eliminated from the lungs is referred to as gas exchange.
Blood–gas interface
Gas exchange takes place at the blood–gas interface , which exists where
the alveoli and the pulmonary capillaries come together. The alveoli are
the smallest airways in the lungs; the pulmonary capillaries are found in
the walls of the alveoli. Inspired oxygen moves from the alveoli into the
capillaries for eventual transport to tissues. Entering the lungs by way of
the pulmonary circulation, carbon dioxide moves from the capillaries into
the alveoli for elimination by expiration. Oxygen and carbon dioxide
move across the blood–gas interface by way of simple diffusion from an
area of high concentration to an area of low concentration.
The blood–gas interface consists of the alveolar epithelium, capillary
endothelium, and interstitium. Taken together, only 0.5µm separates the
air in the alveoli from the blood in the capillaries. The extreme thinness
of the blood–gas interface further facilitates gas exchange by way of
diffusion.
Airways
Air is carried to and from the lungs by the trachea extending toward the
lungs from the larynx. The trachea divides into the right and left main
bronchi; these primary bronchi each supply a lung. The primary bronchi
branch and form the secondary, or lobar, bronchi, one for each lobe of
lung.
The lobar bronchi branch and form the tertiary, or segmental, bronchi ,
one for each of the functional segments within the lobes. These bronchi
continue to branch and move outward toward the periphery of the lungs.
The smallest airways without alveoli are the terminal bronchioles. Taken
together, the airways from the trachea through and including the terminal
bronchioles are referred to as conducting airways.
This region contains no alveoli, so no gas exchange takes place in this
area. Consequently, it is also referred to as anatomical dead space.
The conducting airways carry out two major functions. The first is to
lead inspired air to the more distal gas-exchanging regions of the lungs.
The second is to warm and humidify the inspired air as it flows through
them. The alveoli are delicate structures and may be damaged by
excessive exposure to cold, dry air.
Branching from the terminal bronchioles are the respiratory bronchioles.
This is the first generation of airways to have alveoli in their walls.
Finally, there are the alveolar ducts which are completely lined with
alveolar sacs. This region, from the respiratory bronchioles through the
alveoli, is referred to as the respiratory zone , which comprises most of
the lungs and has a volume of about 3000 ml at the end of a normal
expiration.
All of the conducting airways (trachea through terminal bronchioles) are
lined with pseudostratified ciliated columnar epithelium. Interspersed
among these epithelial cells are mucus-secreting goblet cells.
Furthermore, mucus glands are found in the larger airways.
Consequently, the surface of the conducting airways consists of a mucuscovered ciliated epithelium. The cilia beat upward at frequencies between
600 and 900 beats per minute. As a result, the cilia continuously move the
mucus away from the respiratory zone and up toward the pharynx. This
mucociliary escalator provides an important protective mechanism that
removes inhaled particles from the lungs. Mucus that reaches the pharynx
is usually swallowed or expectorated.
Cartilage. The trachea and primary bronchi contain C-shaped cartilage
Rings in their walls; the lobar bronchi contain plates of cartilage
that completely encircle the airways. The cartilage in these large airways
provides structural support and prevents collapse of the airways. As the
bronchi continue to branch and move out toward the lung periphery, the
cartilage diminishes progressively until it disappears in airways about 1
mm in diameter. Airways with no cartilage are referred to as bronchioles.
As the cartilage becomes more sparse, it is replaced by smooth muscle.
Therefore, the bronchioles, which have no cartilage to support them and
smooth muscle capable of vigorous constriction, are susceptible to
collapse under certain conditions, such as an asthmatic attack.
The pleura
Each lung is enclosed in a double-walled sac referred to as the pleura.
The visceral pleura is the membrane adhered to the external surface of the
lungs. The parietal pleura lines the walls of the thoracic cavity. The space
in between the two layers, the pleural space , is very thin and completely
closed. The pleural space is filled with pleural fluid that lubricates the
membranes and reduces friction between the layers as they slide past each
other during breathing. This fluid also plays a role in maintaining lung
inflation. The surface tension between the molecules of the pleural fluid
keeps the two layers of the pleura “adhered” to each other.
The water molecules pull tightly together and oppose the separation of
the slides. In this way, the lungs are in contact with the thoracic wall, fill
the thoracic cavity, and remain inflated. In other words, surface tension in
the pleural space opposes the tendency of the lungs to collapse.
Mechanics of breathing
The mechanics of breathing involve volume and pressure changes
occurring during ventilation that allow air to move in and out of the
lungs.
Thoracic volume. The volume of the thoracic cavity increases during
inspiration and decreases during expiration.
Inspiration. The most important muscle of inspiration is the diaphragm,
a thin, dome-shaped muscle inserted into the lower ribs. A skeletal
muscle ,it is supplied by the phrenic nerves. When the diaphragm
contracts, it flattens and pushes downward against the contents of the
abdomen. Therefore, contraction of the diaphragm causes an increase in
the vertical dimension of the thoracic cavity and an increase in thoracic
volume.
Assisting the diaphragm with inspiration are the external intercostal
muscles, which connect adjacent ribs. When the external intercostal
muscles contract, the ribs are lifted upward and outward (much like a
handle on a bucket). Therefore, contraction of these muscles causes an
increase in the horizontal dimension of the thoracic cavity and a further
increase in thoracic volume. The external intercostal muscles are supplied
by the intercostal nerves.
Expiration. Expiration during normal, quiet breathing is passive. In other
words, no active muscle contraction is required. When the diaphragm is
no longer stimulated by the phrenic nerves to contract, it passively returns
to its original preinspiration position under the ribs. Relaxation of the
external intercostal muscles allows the rib cage to fall inward and
downward, largely due to gravity. As a result, these movements cause a
decrease in thoracic volume.
Lung volume. No real physical attachments exist between the lungs and
the thoracic wall. Instead, the lungs literally float in the thoracic cavity,
surrounded by pleural fluid. Therefore, the question arises of how the
volume of the lungs increases when the volume of the thoracic cavity
increases.
The mechanism involves the pleural fluid and the surface tension between
the molecules of this fluid. The surface tension of the pleural fluid keeps
the parietal pleura lining the thoracic cavity and the visceral pleura on the
external surface of the lungs “adhered” to each other.
In other words, the pleural fluid keeps the lungs in contact with the chest
wall. Therefore, as the muscles of inspiration cause the chest wall to
expand (thus increasing the thoracic volume), the lungs are pulled open as
well. As a result, lung volume also increases.
Elastic behavior of lungs
In a healthy individual, the lungs are very distensible; in other words,
they can be inflated with minimal effort. Furthermore, during normal,
quiet breathing, expiration is passive. The lungs inherently recoil to their
preinspiratory position. These processes are attributed to the elastic
behavior of the lungs. The elasticity of the lungs involves the following
two interrelated properties:
• Elastic recoil
• Pulmonary compliance
The elastic recoil of the lungs refers to their ability to return to their
original configuration following inspiration. It may also be used to
describe the tendency of the lungs to oppose inflation. Conversely,
pulmonary compliance describes how easily the lungs inflate.
The elastic behavior of the lungs is determined by two factors:
• Elastic connective tissue in the lungs
• Alveolar surface tension
The elastic connective tissue in the lungs consists of elastin and collagen
fibers found in the alveolar walls and around blood vessels and bronchi.
When the lungs are inflated, the connective tissue fibers are stretched, or
distorted. As a result, they have a tendency to return to their original
shape and cause the elastic recoil of the lungs following inspiration.
The alveoli are lined with fluid. At an air–water interface, the water
molecules are much more strongly attracted to each other than to the air
at their surface. This attraction produces a force at the surface of the fluid
referred to as surface tension (ST). Alveolar surface tension exerts
effects on the elastic behavior of the lungs. It decreases the compliance of
the lungs.
Normal lungs, however, produce a chemical substance referred to as
pulmonary surfactant. Made by alveolar type II cells within the
alveoli, surfactant is a complex mixture of proteins and phospholipids ,
the predominant constituent. By interspersing throughout the fluid lining
the alveoli, surfactant disrupts the cohesive forces between the water
molecules. As a result, pulmonary surfactant decreases surface tension.
Ventilation
Ventilation is the exchange of air between the external atmosphere and
the alveoli. It is typically defined as the volume of air entering the alveoli
per minute. A complete understanding of ventilation requires the
consideration of lung volumes.
Standard lung volumes. The size of the lungs and therefore the lung
volumes depend upon an individual’s height, weight or body surface area,
age, and gender. This discussion will include the typical values for a 70kg adult. The four standard lung volumes are:
• Tidal volume
• Residual volume
• Expiratory reserve volume
• Inspiratory reserve volume
The tidal volume (VT) is the volume of air that enters the lungs per
breath. During normal, quiet breathing, tidal volume is 500 ml per breath.
This volume increases significantly during exercise. The residual
volume (RV) is the volume of air remaining in the lungs following a
maximal forced expiration. Residual volume is normally 1.5 l.
Expiratory reserve volume (ERV) is the volume of air expelled from
the lungs during a maximal forced expiration beginning at the end of a
normal expiration. The ERV is normally about 1.5 l. The inspiratory
reserve volume (IRV) is the volume of air inhaled into the lungs during
a maximal forced inspiration beginning at the end of a normal inspiration.
The IRV is normally about 2.5 l.
The four standard lung capacities consist of two or more lung volumes
in combination :
• Functional residual capacity
• Inspiratory capacity
• Total lung capacity
• Vital capacity
The functional residual capacity (FRC) is the volume of air remaining
in the lungs at the end of a normal expiration. The FRC consists of the
residual volume and the expiratory reserve volume and is equal to 3 l.
The inspiratory capacity (IC) is the volume of air that enters the lungs
during a maximal forced inspiration beginning at the end of a normal
expiration (FRC). The IC consists of the tidal volume and the inspiratory
reserve volume and is equal to 3 l. The total lung capacity (TLC) is the
volume of air in the lungs following a maximal forced inspiration. In
other words, it is the maximum volume to which the lungs can be
expanded. It is determined by the strength of contraction of the
inspiratory muscles and the inward elastic recoil of the lungs. The TLC
consists of all four lung volumes and is equal to about 6 l in a healthy
adult male and about 5 l in a healthy adult female.
The vital capacity (VC) is the volume of air expelled from the lungs
during a maximal forced expiration following a maximal forced
inspiration. In others words, it consists of the tidal volume as well as the
inspiratory and expiratory reserve volumes. Vital capacity is
approximately 4.5 l.
Total ventilation. The total ventilation (minute volume) is the volume of
air that enters the lungs per minute. It is determined by tidal volume and
breathing frequency:
Total ventilation = tidal volume × breathing frequency
= 500 ml/breath × 12 breaths/min
= 6000 ml/min
Alveolar ventilation. Alveolar ventilation is less than the total ventilation
because the last portion of each tidal volume remains in the conducting
airways; therefore, that air does not participate in gas exchange.
The volume of the conducting airways is referred to as anatomical dead
space. The calculation of alveolar ventilation includes the tidal volume
adjusted for anatomical dead space and includes only air that actually
reaches the respiratory zone:
Alveolar ventilation
= (tidal volume – anatomical dead space) × breathing frequency
= (500 ml/breath – 150 ml dead space) × 12 breaths/min
= 4200 ml/min
During exercise, the working muscles need to obtain more oxygen and
eliminate more carbon dioxide. Alveolar ventilation is increased
accordingly.
Diffusion
Oxygen and carbon dioxide cross the blood–gas interface by way of
diffusion.
The diffusion of oxygen and carbon dioxide depends on their partial
pressure gradients. Oxygen diffuses from an area of high partial
pressure in the alveoli to an area of low partial pressure in the pulmonary
capillary blood. Conversely, carbon dioxide diffuses down its partial
pressure gradient from the pulmonary capillary blood into the alveoli.
The partial pressure of a gas (Pgas) is equal to its fractional
concentration (% total gas) multiplied by the total pressure (Ptot) of all
gases in a mixture:
Pgas = % total gas × Ptot
The atmosphere is a mixture of gases containing 21% oxygen and 79%
nitrogen. Due to the effects of gravity, this mixture exerts a total
atmospheric pressure (barometric pressure) of 760 mmHg at sea level.
The PO2 of the atmosphere at sea level is 160 mmHg and the PN2 is 600
mmHg. The total pressure (760 mmHg) is equal to the sum of the partial
pressures.
Partial pressures of oxygen and carbon dioxide in the alveoli
As explained in the previous section, the PO2 of the atmosphere is 160
mmHg. The partial pressure of carbon dioxide (PCO2) is negligible. As
air is inspired, it is warmed and humidified as it flows through the
conducting airways. Therefore, water vapor is added to the gas mixture.
The partial pressure of the water vapor is 47 mmHg and, as a result, the
PO2 is slightly decreased to 150 mmHg. The PCO2 remains at 0 mmHg.
By the time the air reaches the alveoli, the PO2 has decreased to about
100 mmHg. The PCO2 of the alveoli is about 40 mmHg.
Oxygen diffuses down its partial pressure gradient from the alveoli into
the pulmonary capillary blood until equilibration is reached, the PO2 of
this blood reaches 100 mmHg. This blood flows back to the left side of
the heart and into the systemic circulation. Therefore, the PO2 of the
arterial blood is 100 mmHg.
Likewise, assuming that carbon dioxide diffuses down its partial pressure
gradient from the pulmonary capillary blood (PCO2 = 45mmHg) into
the alveoli until equilibration is reached, the PCO2 of the blood leaving
these capillaries should be 40 mmHg. Therefore, the PCO2 of the arterial
blood is 40 mmHg.
Gas transport in blood
Transport of oxygen. Oxygen is carried in the blood in two forms:
• Physically dissolved
• Chemically combined with hemoglobin
Oxygen is poorly soluble in plasma. At a PO2 of 100 mmHg, only 3 ml
of oxygen is physically dissolved in 1 l of blood. Assuming a blood
volume of 5 l, a total of 15 ml of oxygen is in the dissolved form. A
normal rate of oxygen consumption at rest is about 250 ml/min. During
exercise, oxygen consumption may increase to 3.5 to 5.5 l/min.
Therefore, the amount of dissolved oxygen is clearly insufficient to meet
the needs of the tissues.
Most of the oxygen in the blood (98.5%) is transported chemically
pcombined with hemoglobin. A large complex molecule, hemoglobin
consists of four polypeptide chains (globin portion), each of which
contains a ferrous iron atom (heme portion). Each iron atom can bind
reversibly with an oxygen molecule:
O2 + Hb ´ HbO2
As the PO2 increases (as it does in the lungs), more will combine with
hemoglobin. When the PO2 decreases, as it does in the tissues consuming
it, the reaction moves to the left and the hemoglobin releases the oxygen.
Each gram of hemoglobin can combine with up to 1.34 ml of oxygen. In a
healthy individual, there are 15 g of hemoglobin per 100 ml of blood.
Therefore, the oxygen content of the blood is 20.1 ml O2/100 ml blood.
Transport of carbon dioxide.
Carbon dioxide is carried in the blood in three forms:
• Physically dissolved
• Carbamino hemoglobin
• Bicarbonate ions
As with oxygen, the amount of carbon dioxide physically dissolved in the
plasma is proportional to its partial pressure. However, carbon dioxide is
20 times more soluble in plasma than is oxygen. Therefore,
approximately 10% of carbon dioxide in blood is transported in the
dissolved form.
Carbon dioxide can combine chemically with the terminal amine groups
(NH2) in blood proteins. The most important of these proteins for this
process is hemoglobin. The combination of carbon dioxide and
hemoglobin forms carbamino hemoglobin:
Hb·NH2 + CO2 ´ Hb·NH·COOH
Deoxyhemoglobin can bind more carbon dioxide than oxygenated
hemoglobin. Therefore, unloading of oxygen in the tissues facilitates
loading of carbon dioxide for transport to the lungs. Approximately 30%
of carbon dioxide in the blood is transported in this form.
remaining 60% of carbon dioxide is transported in the blood in the form
of The bicarbonate ions. This mechanism is made possible by the
following reaction:
The carbon dioxide produced during cellular metabolism diffuses out of
the cells and into the plasma. It then continues to diffuse down its
concentration gradient into the red blood cells. Within these cells, the
enzyme carbonic anhydrase (CA) facilitates combination of carbon
dioxide and water to form carbonic acid (H2CO3). The carbonic acid then
dissociates into hydrogen ion (H+) and bicarbonate ion (HCO3– ).
As the bicarbonate ions are formed, they diffuse down their concentration
gradient out of the red blood cell and into the plasma. This process is
beneficial because bicarbonate ion is far more soluble in the plasma than
carbon dioxide. As the negatively charged bicarbonate ions exit the red
blood cell, chloride ions, the most abundant anions in the plasma, enter
the cells. This process, referred to as the chloride shift, maintains
electrical neutrality. Many of the hydrogen ions bind with hemoglobin.
As with carbon dioxide, deoxyhemoglobin can bind more readily with
hydrogen ions than oxygenated hemoglobin.
This entire reaction is reversed when the blood reaches the lungs.
Because carbon dioxide is eliminated by ventilation, the reaction is pulled
to the left. Bicarbonate ions diffuse back into the red blood cells. The
hemoglobin releases the hydrogen ions and is now available to load up
with oxygen. The bicarbonate ions combine with the hydrogen ions to
form carbonic acid, which then dissociates into carbon dioxide and water.
The carbon dioxide diffuses down its concentration gradient from the
blood into the alveoli and is exhaled.
Regulation of ventilation
The rate and depth of breathing are perfectly adjusted to meet the
metabolic needs of the tissues and to maintain a PO2 of 100 mmHg, a
PCO2 of 40 mmHg, and a pH of 7.4 in the arterial blood.
Breathing is initiated spontaneously by the central nervous system and
occurs in a continuous cyclical pattern of inspiration and expiration. The
three major components of the regulatory system for ventilation are:
• Medullary respiratory center
• Receptors and other sources of input
• Effector tissues (respiratory muscles)
Aggregates of cell bodies within the medulla of the brainstem form the
medullary respiratory center, which has two distinct functional areas:
• Dorsal respiratory group
• Ventral respiratory group
The aggregate of cell bodies in the dorsal region of the medulla is the
dorsal respiratory group (DRG). The DRG consists primarily of
inspiratory neurons. These neurons are self-excitable and repetitively
generate action potentials to cause inspiration. The inspiratory neurons
descend to the spinal cord where they stimulate neurons that supply the
inspiratory muscles, including those of the phrenic nerves and the
intercostal nerves. These nerves then stimulate the diaphragm and the
external intercostal muscles to contract and cause inspiration.
When the inspiratory neurons are electrically inactive, expiration takes
place. Therefore, this cyclical electrical activity of the DRG is responsible
for the basic rhythm of breathing. Furthermore, the DRG is likely the site
of integration of the various sources of input that alter the spontaneous
pattern of inspiration and expiration.
The aggregate of cell bodies in the ventral region of the medulla is the
ventral respiratory group (VRG). The VRG consists of expiratory and
inspiratory neurons. This region is inactive during normal, quiet
breathing. (Recall that expiration at this time is a passive process.)
However, the VRG is active when the demands for ventilation are
increased, such as during exercise.
Under these conditions, action potentials in the expiratory neurons cause
forced, or active, expiration. These neurons descend to the spinal cord
where they stimulate the neurons that supply the expiratory muscles,
including those that innervate the muscles of the abdominal wall and the
internal intercostal muscles. Contractions of these muscles cause a more
rapid and more forceful expiration.
Inspiratory neurons of the VRG augment inspiratory activity. These
neurons descend to the spinal cord where they stimulate neurons that
supply the accessory muscles of inspiration including those that innervate
the scalenus and sternocleidomastoid muscles. Contractions of these
muscles cause a more forceful inspiration.
In summary, the regulation of ventilation by the medullary respiratory
center determines the:
• Interval between the successive groups of action potentials of the
inspiratory neurons, which determines the rate or frequency of breathing
(as the interval shortens, the breathing rate increases)
• Frequency of action potential generation and duration of this electrical
activity to the motor neurons, and therefore the muscles of inspiration
and expiration, which determines the depth of breathing, or
the tidal volume (as the frequency and duration of stimulation increase,
the tidal volume increases)
The medullary respiratory center receives excitatory and inhibitory inputs
from many areas of the brain and peripheral nervous system, including:
• Lung receptors
• Proprioceptors
• Pain receptors
• Limbic system
• Chemoreceptors