1. BIOMECHANICS OF
RESPIRATORY ACT.
2. VENTILATION OF LUNGS.
3. Regulation of respiration.
BIOMECHANICS OF RESPIRATORY ACT
Common
characteristic of breathing. The
respiratory system is divided into a respiratory zone, which is the site of gas
exchange between air and blood, and a conducting zone, which conducts the air
to the respiratory zone. The exchange of gases between air and blood occurs across
the walls of tiny air sacs called alveoli, which are only a single cell layer
thick to permit very rapid rates of gas diffusion.
The term
respiration includes three separate but related functions:
(1) ventilation (breathing);
(2) gas exchange, which occurs between
the air and blood in the lungs and between the blood and other tissues of the
body; and
(3) oxygen utilization by the tissues
in the energy – liberating reactions of cell respiration.
Breathing
Basics. With each breath, we bring oxygen
into the lungs. When we exhale, we release carbon dioxide (CO2), water, and
other gases from the lungs. The balance of CO2 and oxygen in the blood is very
important to general health. By altering your breathing, you can change this
balance and cause other physical and mental symptoms. Breathing engages various
parts of the body to expand the lungs. The primary muscle of breathing is the
diaphragm.6, 7 As the
diaphragm flattens downward when you inhale (also known as inspiration), the
chest cavity expands and air is drawn into the lungs.
Work of Breathing
Work = Pressure x Volume
Respiratory work at rest or during
exercise is seldom responsible for more than 5% of the total body work. Most of
this is used to overcome the lung and chest wall stiffness during inspiration.
Work to overcome airway resistance is usually very small, except during
exercise or in athsmatics.
Patients with most respiratory diseases
have increased respiratory workloads, which may be due to high respiratory
rates, stiff lungs, or high airway resistances. When the patient becomes so
exhausted that they can no longer keep up the workload, respiratory failure
ensues. Anaesthetic machine tubing, one-way valves, and ETTs all increase total
resistance and respiratory work, while drugs will diminish respiratory effort,
so that the patient with poor respiratory function usually requires ventilating
both during and after the operation.
Ventilation
and the exchange of gases (oxygen and carbon dioxide) between the air and blood
are collectively called external respiration. Gas exchange between the blood
and other tissues and oxygen utilization by the tissues are collectively known
as internal respiration.
Ventilation
is the mechanical process that moves air into and out of the lungs. Since the
oxygen concentration of air is higher in the lungs than in the blood, oxygen
diffuses from air to blood. Carbon dioxide conversely moves from the blood to
the air within the lungs by diffusing down its concentration gradient. As a
result of this gas exchange, the inspired air contains more oxygen and less
carbon dioxide than the expired air. More importantly blood leaving the lungs
(in the pulmonary veins) has a higher oxygen and lower carbon dioxide
concentration than the blood delivered to the lungs in the pulmonary arteries. This result bring the fact that
lungs function is to give gaseous equilibrium between blood and the air.
Main process of the external respiration. The passage
air respiratory systems are divided into two functional zones. The respiratory
zone is the region where gas exchange occurs,
it includes the respiratory bronchioles (which contain separate outpouchings of
alveoli) and the terminal cluster of alveolar sacs.
The
conducting zone of the respiratory system, in summary, consists of the mouth,
nose, pharynx, larynx, trachea, primary bronchi, and all successive branchings
of the bronchioles up to and including the terminal bronchioles. In addition to
conducting air into the respiratory zone, these structures serve additional
functions: warming and humidification of the inspired air and filtration
and cleaning. Regardless of the
temperature and humidity of the ambient air, when the inspired air reaches the
respiratory zone it is at a temperature of 37° C (body temperature), and it is
saturated with water vapor as it flows over the warm, wet mucous membranes that
line the respiratory airways. This ensures that a constant internal body
temperature will be maintained and that delicate lung tissue will be protected
from desiccation.
Gas exchange between the air and blood occurs entirely by diffusion
through lung tissue. This diffusion occurs very rapid because
there is a large surface area within the lungs and a very short diffusion
distance between blood and air.
Phases of respiratory act. Inspiration & Expiration
Pulmonary
ventilation consists of two phases: inspiration and expiration. Inspiration
(inhalation) and expiration (exhalation) are accomplished by alternately
increasing and decreasing the volume of the thorax and lungs.
The thorax
must be sufficiently rigid so that it can protect vital organs and provide
attachments for many short and powerful muscles. Breathing, or pulmonary
ventilation, requires the flexibility of the thorax to function as a bellow
during the ventilation cycle. The rigidity and the surfaces for muscle
attachment are provided by the bony composition of the rib cage.
he rib cage is
pliable, because the ribs are separate from one another and most of the ribs
(upper ten of the twelve pairs) are attached to the sternum by resilient costal
cartilages. The vertebral attachments also provide considerable mobility. The
structure of the rib cage and associated cartilages provides continuous elastic
tension, so that after stretched by muscle contraction during inspiration, the
rib cage can return passively to its resting dimension when the muscles relax.
This elastic recoil is greatly aided by the elasticity of the lungs.
Respiratory
muscles cause passage of air into the Lung. Between the bony portions of the
rib cage are two layers of intercostals muscles: the external intercostal
muscles and internal intercostal muscles. Between the costal cartilages, there
is only one muscle layer, which its fibers oriented in the same manner to those
of the internal intercostal muscle. These muscles may called as the interchondral part of the internal
intercostal muscle or parasternal intercostal muscle.
An unforced,
or quiet, inspiration primarily results from contraction of the dome– shaped
diaphragm, which become lowered and flattened. This increases thoracic volume
in a vertical direction. Inspiration is also aided by the parasternal and
external intercostal muscles, which raise the ribs when they contract and
increase thoracic volume laterally. Other thoracic muscles involved in forced
(deep) inspiration. The most important of these is the scalenus muscle,
followed by the pectoralis minor muscle, and in extreme cases the
sternocleidomastoid muscle. Contraction of these muscles elevates the ribs in
an anteroposterior direction; simultaneously, the upper rib cage is stabilized
so that the intercostal muscles become more effective.
Mechanism of normal
quiet inspiration and expiration.
Quiet inspiration is an active process. The contraction of the inspiratory
muscles and diaphragm increases intrathoracic volume. This stretch the thorax
and lungs. Quiet expiration is a passive process. The thorax and lungs recoil
when the respiratory muscles relax. due
to their elastic tension
During quiet
breathing, the intrapleural pressure, which is about -
Mechanism
forced ventilation. Strong inspiratory efforts reduce the intrapleural pressure
value as low as —30 mm Hg, producing correspondingly greater degrees of lung
inflation. When forced ventilation is increased, the extent of lung
deflation is also increased by active contraction of expiratory muscles that
decrease intrathoracic volume.
Movement of
the diaphragm accounts for 75% of the change in intrathoracic volume during
quiet inspiration. This muscle attached around the bottom of the thoracic cage,
and it arches over the liver and moves downward like a piston when it
contracts.
The other
important inspiratory muscles are the external intercostals muscles, which run
obliquely downward and forward from rib to rib. The ribs pivot as if hinged at
the back, so that when the external intercostals contract they elevate the
lower ribs. This pushes the sternum outward and increases the anteroposterior
diameter of the chest. The transverse diameter is actually changed little if at
all. Either the diaphragm or the external intercostals muscles alone can
maintain adequate ventilation at rest. Transaction of the spinal cord above the
third cervical segment cause fatal without artificial respiration, but
transaction below the origin of the phrenic nerves that innervate the diaphragm
(third to fifth cervical segments) is not fatal; conversely, in patients with
bilateral phrenic nerve palsy, respiration is somewhat labored, but
adequate to maintain life. The scalene and sternocleidomastoid muscles in the
neck are accessory inspiratory muscles that they help to elevate the thoracic
cage during deep labored respiration.
A decrease in intrathoracic volume
and forced expiration result when the expiratory muscles contract. The internal
intercostals have this action because they pass obliquely downward and
posterior from rib to rib and therefore pull the rib cage downward when they
contract. Contractions of the muscles of the anterior abdominal wall also aid
expiration by pulling the rib cage downward and inward and by increasing the
intraabdominal pressure, which pushes the diaphragm upward.
Change of
pressure in pleural cavity in correlation from phases of respiratory act. The
lungs and the chest wall are elastic structures. Normally, there is no more
than a thin layer of fluid between the lungs and the chest wall. The lungs
slide easily on the chest wall but resist being pulled away from it in the same
way as 2 moist pieces of glass slide on each other but resist
separation. The pressure in the "space" between the lungs and chest
wall (intrapleural pressure) is sub atmospheric. The lungs are stretched when they
are expanded at birth, and at the end of quiet expiration their tendency to
recoil from the chest wall is just balanced by the tendency of the chest wall
to recoil in the opposite direction. If the chest wall is opened, the lungs will
collapse; and if the lungs lose their elasticity, the chest expands and becomes
barrel-shaped.
Movement of blood on venous in
correlation from phases of respiratory act.
Contraction
of the diaphragm during inhalation also improves venous return. As the
diaphragm contracts, it lowers to increase the thoracic volume and decrease the
abdominal volume. This creates a partial vacuum in the thoracic cavity
(negative intrathoracic pressure) and a higher pressure in the abdominal
cavity. The pressure difference thus produced favors blood flow from abdominal
to thoracic veins.
Change of
pressure in alveoli. The respiratory muscles cause pulmonary ventilation by
alternatively compressing and distending the lungs, which in turn causes the
pressure in the alveoli to rise and fall. During inspiration the intra-alveolar
pressure becomes slightly negative with respect to atmospheric pressure,
normally slightly less than
During
maximum expiratory effort (with the glottis closed )the intra-alveolar pressure
can be increased to as much as
Intra-alveolar pressure
during inspiration & expiration
As the external intercostals &
diaphragm contract, the lungs expand. The expansion of the lungs causes the
pressure in the lungs (and alveoli) to become slightly negative relative to
atmospheric pressure. As a result, air moves from an area of higher pressure
(the air) to an area of lower pressure (our lungs & alveoli). During
expiration, the respiration muscles relax & lung volume descreases. This
causes pressure in the lungs (and alveoli) to become slight positive relative
to atmospheric pressure. As a result, air leaves the lungs.
The visceral and parietal pleurae are normally
flush against each other, so that the lungs are stuck to the chest wall in the
same manner as two wet pieces of glass sticking to each other. The intrapleural
space contains only a film of fluid secreted by the two membranes. The
pleural cavity in a healthy person is thus potential rather than real; it can
become real only in abnormal situations when air enters the intrapleural space.
Since the lungs normally remain in contact with the chest wall, they expand and
contract along with the thoracic cavity during respiratory movements.
Air enters the lungs during inspiration because
the atmospheric pressure is greater than the intrapulmonary, or intraalveolar,
pressure. Since the atmospheric pressure does not usually change, the
intrapulmonary pressure must fall below atmospheric pressure to cause
inspiration. A pressure below that of the atmosphere is called a subatmospheric
pressure, or negative pressure. During quiet inspiration, for
example, the intrapulmonary pressure may decrease to 3 mmHg below the pressure
of the atmosphere. This subatmospheric pressure is shown as –3 mmHg.
Expiration, conversely, occurs when the intrapulmonary pressure is greater than
the atmospheric pressure. During quiet expiration, for example, the
intrapulmonary pressure may rise to at least +3 mmHg over the atmospheric
pressure.
The lack of air in the intrapleural space
produces a subatmospheric intrapleural pressure that is lower than the
intrapulmonary pressure .
There is thus a pressure difference across the wall of the lung—called the transpulmonary
(or transmural) pressure—which is the difference between the
intrapulmonary pressure and the intrapleural pressure. Since the pressure
within the lungs (intrapulmonary pressure) is greater than that outside the
lungs (intrapleural pressure), the difference in pressure (transpulmonary
pressure) keeps the lungs against the chest wall. Thus, the changes in lung
volume parallel changes in thoracic volume during inspiration and expiration.
Recoil
Tendency of the Lungs, and the Intrapleural Pressure. The lungs have a
continual elastic tendency to collapse and therefore to pull away from the chest
wall. This is called the recoil tendency of the lungs, and it is caused by two
different factors. First, throughout the lungs are many elastic fibers that are
stretched by lung inflation and therefore attempt to shorten. Second, and even
more important, the surface tension of the fluid lining the alveoli also causes
a continual elastic tendency for the alveoli to collapse. This effect is caused
by intermolecular attraction between the surface molecules of the alveolar
fluid. That is, each molecule pulls on the next one so that the whole lining
sheet of fluid on the alveolar surfaces acts like many small elastic balloons
continuously trying to collapse the lung.
Ordinarily,
the elastic fibers in the lungs account for about one third of the recoil
tendency, and the surface tension phenomenon accounts for about two thirds.
The total
recoil tendency of the lungs can be measured by the amount of negative pressure
in the pleural space required to prevent collapse of the lungs; this pressure
is called the pleural pressure or, occasionally, the lung recoil pressure. It
is normally about -
"Surfactant" in the alveoli,
and its effect on the collapse tendency.
A lipoprotein
mixture called "surfactant" is secreted by special surfactant-secreting
cells (the "type II granular pneumocytes") which are the component
parts of the alveolar epithelium. This mixture, containing especially the
phospholipids dipalmitoyl lecithin, decreases the surface tension of the
alveolar fluid lining. In the absence of surfactant, lung expansion is
extremely difficult, which often requires negative pleural pressures as low as
- 20 to -
Surfactant is produced by type II alveolar
cells in late fetal life. Premature babies are sometimes born with lungs that
lack sufficient surfactant, and their alveoli are collapsed as a result. This
condition is called respiratory distress syndrome (RDS). Considering
that a full-term pregnancy lasts 37 to 42 weeks, RDS occurs in about 60% of
babies born at less than 28 weeks, 30% of babies born at 28 to 34 weeks, and
less than 5% of babies born after 34 weeks of gestation. The risk of RDS can be
assessed by analysis of amniotic fluid (surrounding the fetus), and mothers can
be given exogenous corticosteroids to accelerate the maturation of their
fetus’s lungs.
Control
of Bronchial Tone
The walls of
bronchi and bronchioles contain smooth muscle and they are innervated by the
autonomic nervous system. In general, sympathetic discharge via
Beta-2-adrenergic receptors causes the bronchi to dilate and parasympathetic
discharge via the vagus nerves causes them to constrict.. It may be similar to the intrinsic enteric nervous
system in the gastrointestinal tract and there is evidence that VIP (Vasoactive
intestinal polypeptide) is the mediator secreted by its neurons.
The function
of the bronchial muscles is still a matter of debate, but in general, they
probably help to maintain an even distribution of ventilation. They also
protect the bronchi during coughing. There is a circadian rhythm in bronchial
tone, with maximal constriction at about
Lung Volumes. The amount
of air that moves into the lungs with each inspiration (or the amount that
moves out, with each expiration)
is called the tidal volume. The air inspired with a maximal inspiratory effort
in excess of the tidal volume is the inspiratory reserve volume. The volume
expelled by an active expiration effort after passive expiration is the
expiratory reserve volume, and the air left in the lungs after a maximal
expiratory effort is the residual volume. Normal values for these lung volumes,
and names applied to combinations of them.
1. Tidal volume (TV),
2. Inspiratory reserve volume
(IRV).
3. Expiratory reserve volume
(ERV).
4. Vital capacity (VC)
|
Volume (L) |
||||
|
|
Men |
Women |
|
|
|
Vital capacity (VC) |
IRV |
3.3 |
1.9 |
Inspiratory capacity |
|
TV |
0.6 |
0.5 |
||
|
ERV |
1.0 |
0.7 |
Functional residual capacity |
|
|
RV |
1.2 |
1.1 |
||
|
Total lung capacity |
|
|
|
|
The space in
the conducting zone of the airways occupied by gas that does not exchange with
blood in the pulmonary vessels is the respiratory dead space. The vital
capacity, the greatest amount of air that can be expired after a maximal
inspiratory effort, is frequently measured clinically as an index of pulmonary
function. The fraction of the vital capacity expired in 1 second (timed vital
capacity; also called forced expired volume in 1 second, or FEV I”) gives
additional valuable information. The vital capacity may be normal but the timed
vital capacity can be greatly reduced in diseases such as asthma, in which the
resistance of the airways is increased due to bronchial constriction. The
amount of air inspired per minute (pulmonary ventilation, respiratory minute
volume) is normally about
Spirograph
Effects of Gravity on the Lung.
Because of gravitational forces,the
pressure gradient present. Intrapleural pressure at the bases of the lungs is
Gravity also
affects the pressure in the pulmonary blood vessels. Dead Space &Uneven Ventilation. Since gaseous
exchange in the respiratory system occurs only in the terminal portions of the
airways, the gas that occupies the rest of the respiratory system is not
available for gas exchange with pulmonary capillary blood. Thus, in a man who
weighs
It is wise to
distinguish between the anatomic dead space (respiratory system volume
exclusive of Alveoli) and the total (physiologic) dead space (volume of
gas which do not equilibrate
with blood and air, e.g waste ventilation). In health, the 2 dead spaces
are identical. In disease states that may be no exchange of gas between the
alveoli and the blood, and some of the alveoli may be overventilated.
The volume of
gas in nonperfused alveoli and any volume of air in the alveoli in excess of
that necessary to arterialize the b1ood in the alveolar capillaries is part of
the dead space (no equilibrating) gas volume. The anatomy dead space can be
measured by analysis of the single breath N2 curves. From mid inspiration,the
subject take a deep breath as possible of pure O2, then exhales
steadily while the N2 content of the expired gas is continuously
measured. The initial gas exhaled (phase I) is the gas that filled the dead
space and that consequently contains no N2.
Alveolar Ventilation. Because of
the dead space, the amount of air reaching the alveoli (alveolar ventilation)
at a respiratory minute volume of 6 L/min is 500 minus 150 ml times 12
breath/min, or 4.2 L/min. because of the dead space, rapid, shallow respiration
produces much less alveolar ventilation than slow, deep respiration at the same
respiratory minute volume (Table ).
Table . Effect
of variations in respiratory rate and depth on alveolar ventilation.
|
Respiratory rate |
30/min |
10/min |
|
Tidal volume |
200 ml |
600ml |
|
Minute volume |
|
|
|
Alveolar, ventilation |
(200-150)x30 = 1500 ml |
(600-150)x10=4500ml |
During respiration, air becomes saturated with
water vapor by the time it enters the alveolar sac. In the alveolus, it also
mixes with carbon dioxide.
At the alveolar membrane, each gas diffuses in
the direction where the partial pressure of that gas is less. In other words,
oxygen diffuses towards the blood and is taken up by hemoglobin, and carbon
dioxide diffuses towards the alveolus and mixes with the air. No “active
process” is involved. Oxygen simply diffuses through the membrane and plasma,
and is taken up by the red blood cells.
Although the diffusion occurs very rapidly,
the gases do not have time to totally equilibrate. There will be a small
pressure difference across the alveolar membrane for each gas. That is, oxygen
partial pressure will be somewhat higher in the alveolus than in the blood, and
carbon dioxide pressure will be slightly higher in the blood than in the air in
the alveolus. In the case of oxygen, this pressure difference is calculated for
the lung as a whole as the “arterial-alveolar (Aa) gradient.”
About 2% of the blood flow through the lungs
bypasses the pulmonary capillaries. This blood is not oxygenated, and forms a “physiologic
shunt.” Because of this blood that bypasses the alveoli, arterial blood will always contain less
oxygen pressure than blood that has equilibrated with the oxygen in the lung
alveoli. This “shunt” becomes part of the calculated “Aa gradient.”
As blood circulates through the body, an
opposite change occurs in the capillaries of the systemic circulation. Oxygen
diffuses from the area of higher pressure — the blood — into the lower pressure
of the cells. Carbon dioxide diffuses from the cells into the blood.
The exchange of gases (O2 & CO2) between the alveoli &
the blood occurs by simple diffusion: O2 diffusing from the alveoli into the
blood & CO2 from the blood into the alveoli. Diffusion requires a
concentration gradient. So, the concentration (or pressure) of O2 in the
alveoli must be kept at a higher level than in the blood & the
concentration (or pressure) of CO2 in the alveoli must be kept at a lower lever
than in the blood. We do this, of course, by breathing - continuously bringing
fresh air (with lots of O2 &
little CO2) into the lungs & the alveoli.
Breathing is an active process - requiring the
contraction of skeletal muscles. The primary muscles of respiration include the
external intercostal muscles (located between the ribs) and the diaphragm (a
sheet of muscle located between the thoracic & abdominal cavities).
The influence of cutting of vagal nerves on breathing.
Fix a narcotized rat on the operation table. Make a longitudinal incision of
skin on middle neck line, preparation the vagal nerve. Record the pneumogramme
before and after cutting one and than both of vagal nerves. Draw the results in
your reports. In conclusion explain the changes.
Therefore, the
pressure exerted by any one gas in a mixture of gases (its partial pressure) is
equal to the total pressure times the fraction of the total amount of gas it
represents.
The
composition of dry air is 20.98% O2, 0.04 CO2,
78.06% N2, and 0.92% other inert constituent such as argon and
helium. The barometric pressure (pb)
at sea level is
Cell membranes are completely permeable to the passage
of carbon dioxide and oxygen. On diffusing into the red blood cell these gases
interact with other compounds. Once beyond the capillaries no further gain or
loss of these gases can occur and the compounds involved reach an equilibrium.
While in the systemic capillaries, the RBCs are
subjected to increasing levels of carbon dioxide and decreasing levels of
oxygen. The opposite is the case in the pulmonary capillaries. The reactions
are the same but in reverse directions in these two locations.
Mechanics of Ventilation Air is
delivered to alveoli as a consequence of respiratory muscle contraction. These
muscles include the diaphragm and the external intercostal muscles of the rib
cage and accessory inspiratory muscles (scalenes and sternocleidomastoids which
are not active in eupnea). Contraction of these muscles enlarges the thoracic
cavity, creating a subatmospheric pressure in the alveoli. Contraction of the
diaphragm leads to downwards displacement of the thoracic cavity and
contraction of external intercostals muscles leads to lifting of the thoracic
cage leading to increase in the antero-posterior diameter.
As alveolar
pressure declines, atmospheric air moves into the alveoli by bulk
flow until the pressure is equalized.
The process of inflating the lung is called
inspiration. Expiration is usually
passive, resulting from relaxation of the inspiratory muscles and powered by
elastic recoil of lung tissue that is stretched during inspiration. With
relaxation of the inspiratory muscles and lung deflation, alveolar pressure
exceeds atmospheric pressure, so gases flow from the alveoli to the atmosphere
by bulk flow. Active expiration is due to internal intercostals muscles and the
abdominal recti muscles.
The Opposing Force of Pulmonary
Elastance or Compliance
The lung is an elastic structure with an
anatomical organization that promotes its collapse to essentially zero volume,
much like an inflated balloon. The term elastic means a material deformed by a
force tends to return to its initial shape or configuration when the force is
removed. While the elastic properties of the
lung are important to bring about expiration,
they also oppose lung inflation.
As a result, lung inflation depends upon
contraction of the inspiratory muscles.
The resistance to deformation
(inflation) is termed elastance. However, compliance is the preferred term to
describe the elastic properties of the lung. Compliance, as the recripocal of
elastance, is a measure of the ease of deformation (inflation).
Effect of ventilation perfusion ratio on
alveolar gas concentration:
Ventilation-perfusion ratio (ranges from
0 to infinity):
- Alveolar Oxygen and Carbon Dioxide
Partial Pressures when VA/Q Equals Zero, that is, without any alveolar
ventilation-the air in the alveolus comes to equilibrium with the blood oxygen
and carbon dioxide because these gases diffuse between the blood and the alveolar
air. Because the blood that perfuses the capillaries is venous blood returning
to the lungs from the systemic circulation, it is the gases in this blood with
which the alveolar gases equilibrate. The normal venous blood has a PO2 of
- Alveolar Oxygen and Carbon Dioxide
Partial Pressures when VA/Q Equals Infinity, there is no capillary blood flow
to carry oxygen away or to bring carbon dioxide to the alveoli. Therefore,
instead of the alveolar gases coming to equilibrium with the venous blood, the
alveolar air becomes equal to the humidified inspired air. That is, the air
that is inspired loses no oxygen to the blood and gains no carbon dioxide from
the blood. And because normal inspired and humidified air has a PO2 of
- Gas Exchange and Alveolar Partial
Pressures when VA/Q Is Normal, when there is both normal alveolar ventilation
and normal alveolar capillary blood flow (normal alveolar perfusion), exchange
of oxygen and carbon dioxide through the respiratory membrane is nearly
optimal, and alveolar PO2 is normally at a level of
VA/Q = 0→ O2 = 40, CO2 = 45mmHg
VA/Q = infinity → O2 = 149, CO2 =
0mmHg
VA/Q = normal → O2 = 104, CO2 =
40mmHg
If less than normal then called
physiological shunt If more than normal then called physiological dead space
Normally at the tip of the lung, VA/Q is
(2.5) times normal (phys. dead space), while at the base, it is (0.6) times
normal (phys. shunt).
Normally, there are abnormal VA/Q ratios
in the upper and lower portions of the lung. In the upper both ventilation and
perfusion are low but VA is more than Q, so there is physiological dead space,
but in the lower VA is less than Q, so there is physiological shunt.
Entering the
alveolar capillaries P.O2 =
The exchange of oxygen and carbon
dioxide takes place in between the lungs and blood. The greater part of oxygen
diffuses into the blood and at the same time, carbon dioxide diffuses out. Here
the question is where the oxygen would go.
The
most part oxygen (about 97%) is now carried by the erythrocytes or R. B. Cs.
In which it combines with the hemoglobin, the iron containing respiratory
pigment under high concentration forming loose chemical compound the
oxy-hemoglobin.
Hemoglobin is purple colored but
oxy-hemoglobin is of bright red color. Along the blood stream during
circulation, the oxy-hemoglobin reaches the tissues, breaks up releasing most
of its oxygen, and regains its normal purple color as hemoglobin, there by the
blood acts as an efficient oxygen carrier.
A small portion of oxygen (about 3%)
also dissolves in the plasma and is carried in the form of solution to the
tissues blood stream. Now this free oxygen, before entering into the tissue
proper first passes into the tissue fluid and then enters the tissue by
diffusion. In return, the carbon dioxide is given out by the tissues, dissolves
in the tissue fluid and finally passes into the blood stream and conveyed of
blood is 10 to 26 volumes of oxygen per 100 volumes of blood.
The oxygen transport from lungs to
tissues is achieved because hemoglobin has the highest affinity for oxygen at
While
in the alveolar capillaries, the diffusion of gasses occurs: oxygen diffuses
from the alveoli into the blood & carbon dioxide from the blood into the
alveoli.
Leaving
the alveolar capillaries
§
PO2 =
§
PCO2 =
Figure. Partial pressure and diffusion at the respiratory membrane.
Oxygen moves
from the alveoli to the red blood cells along the short path. The PO2
of alveolar air is
The diffusion
capacity of the lungs for O2 is the amount of O2 that
crosses the alveolar membrane per minute per mm Hg difference in PO2 between the alveolar gas and the blood in the pulmonary
capillaries. Expressed in terms of STPD, it is normally about 20 ml/min/mm Hg
at rest. As a result of capillary dilatation and an increase in the number of
active capillaries, it rises to values of 65 or more during exercise. The
diffusion capacity for O2 is decreased in diseases such as
sarcoidosis and beryllium poisoning (berylliosis) that cause fibrosis of the
alveolar walls and produce alveolar-capillary block.
The P.CO2
of venous blood is
The partial
pressure gradients for O2 and CO2 have been plotted in
graphic form in Fig 44-3 to emphasize that they are the key to gas movement and
that O2 "flows downhill" from the air through the alveoli
and blood into the tissues whereas CO2 ''flows downhill" from
the tissues to the alveoli.
However, the
amount of both of these gases transported to and from the tissues would be
grossly inadequate if it were not that about 99% O2 which
dissolves in the blood combines with the O2 carrying protein hemoglobin
and that about 94% of the CO2 which dissolves enters into a
series of reversible chemical reactions, which convert it into other compounds.
The presence of hemoglobin increases the O2 carrying capacity of the
blood 70-fold, and the reactions of CO2 increase the blood CO2
content 17-fold.
Oxygen Delivery to the Tissues. The O2 delivery system in
the body consists of the lungs and the cardiovascular system. O2
delivery to a particular tissue depends on the amount of O2 entering
the lungs, the adequacy of pulmonary gas exchange, the blood flow to the
tissue, and the capacity of the blood to carry O2. The blood flow
depends on the degree of constriction of the vascular bed in the tissue and the
cardiac output. The amount of O2 in the blood is determined by the
amount of dissolved O2, the amount of hemoglobin in the blood, and
the affinity of the hemoglobin for O2.
How are oxygen & carbon dioxide transported in the blood?
·
Oxygen is carried in blood:
1 - bound to
hemoglobin (98.5% of all oxygen in the blood)
2 - dissolved in the
plasma (1.5%)
Because almost all oxygen in the blood is transported by hemoglobin, the
relationship between the concentration (partial pressure) of oxygen and
hemoglobin saturation (the % of hemoglobin molecules carrying oxygen) is an
important one.
Reaction of The relationship between oxygen
levels and hemoglobin saturation is indicated by the oxygen-hemoglobin dissociation (saturation)
curve(in the graph above). You can see that at high partial pressures of O2
(above about
Recall that
When you do become more active, partial pressures of
oxygen in your (active) cells may drop well below
Myoglobin.
Myoglobin is an iron-containing pigment found in skeletal muscle. It resembles
hemoglobin but binds one rather than 4 mol of O2 per mole. Its
dissociation curve is a rectangular hyperbola rather than a sigmoid curve.
Because its curve is to the left of the hemoglobin curve (Fig), it takes
up O2 from hemoglobin in the blood.
It releases O2
only at low P.O2 values,
but the P O2 in exercising muscle is close to zero. The myoglobin
content is greatest in muscles specialized for sustained contraction.
The muscle blood
supply is compressed during such contractions, and myoglobin may provide
O2 when blood flow is cut off. There is also evidence that myoglobin
facilitates the diffusion of O2 from the blood to the mitochondria,
where the oxidative reactions occur.
REGULATION OF RESPIRATION
Respiration is
regulated by two mechanisms:Nervous
or neural mechanismChemical mechanismNervous Mechanism: It involves respiratory
centers, afferent and efferent nerves.
Respiratory
centers:
The
centres in the medulla oblongata and pons that collects sensory information
about the level of oxygen and carbon dioxide in the blood and determines the
signals to be sent to the respiratory muscles.Stimulation of these respiratory
muscles provide respiratory movements which leads to alveolar
ventilation.Respiratory centers are situated in the reticular formation of the
brainstem and depending upon the situation in brainstem, the respiratory
centers are classified into two groups: Medullary centers Pontine center
s
There are two
centers in each group: Medullary Centers:
Inspiratory
center
Expiratory
center
Pontine Centers:
Pneumotaxic centerApneustic center
Inspiratory
center:
Inspiratory
center is situated in upper part of medulla oblongataThis center is also called
dorsal group of respiratory neuronsIt is formed by nucleus of tractus
solitariusFunction: it is concerned with inspiration.
Expiratory
center:
It is situated
in medulla oblongata anterior and lateral to the inspiratory centerIt is also
called ventral group of respiratory neuronsIt is formed by neurons of nucleus
ambiguous and nucleus retro ambiguous Function: this center is inactive during
quiet breathing and inspiratory center is the active center, but during forced
breathing or when the inspiratory center is inhibited it becomes active.
Pneumotaxic center:
It is situated
in upper Pons.It is formed by nucleus parabrachialis.Function: it controls
medullary respiratory centers, particularly the inspiratory center through
apneustic center. It always controls the activity of inspiratory center so that
duration of inspiration is controlled.Apnuestic center:It is situated in lower Pons.Function: this center
increases depth of inspiration by acting directly on the inspiratory center.
Nervous
connections of respiratory centers:
Afferent
pathway:
Respiratory center
receive afferent impulses from different parts of the body according to
movements of thoracic cage and lungs.From peripheral chemoreceptor and
baroreceptor impulses are carried by glossopharyngeal and vagus nerves to
respiratory center.
Efferent pathway:
Nerve fiber from respiratory center leaves the brain
and descend in anterior part of lateral column of spinal cord.
These nerve fibers terminate in the motor neurons in the anterior horn cells of
the cervical and thoracic segments of spinal cord. From motor neurons two sets
of nerve fiber arise which
supplies particular muscle:
Phrenic nerve
fibers: supplies diaphragm The
intercostal nerve fibers: supplies intercostal muscles.
Factors
affecting respiratory centers:
Impulses from
higher centers: impulses from higher center can stimulate or inhibit
respiratory centers directly.
Impulses from
Thermoreceptors:
Thermoreceptors
give response to change in the body temperature.They are cutaneous receptors
namely cold and warmthWhen this receptors get stimulated they send signals to
cerebral cortexCerebral cortex in turn stimulates respiratory centres and
causes hyperventilation.
Impulses from
pain receptors: Pain receptors give response to pain stimulus.Like
other receptors this
receptors also send impulses to the cerebral cortex.Cerebral cortex in turn
stimulates the respiratory centers ad causes hyperventilation.
Cough reflex: This is a
protective reflex caused by irritation of parts of the respiratory tract beyond
nose like larynx, trachea and bronchi.Irritation of any of this part causes
stimulation of vagus nerve and cough occurs.Cough begins with deep inspiration
followed by forceful expiration with closed glottis.So the intrapleural
pressure rises above
Sneezing reflex:
It is also a
protective reflex which occurs due to the irritation of nasal mucus
membrane.During irritation of nasal mucus membrane, the olfactory receptors and
trigeminal nerve endings present in the nasal mucosa are stimulated leading to
sneezing.Sneezing starts with deep inspiration, followed by forceful expiratory
effort with opened glottis and the irritants are expelled out of the
respiratory tract.
Deglutition
reflex:
During
swallowing of the food, the respiration is arrested for a while.Temporary
arrest of the respiration is called apnea and apnea which occurs during
swallowing called swallowing apnea or deglutition apnea.This prevents entry of
the food particles into the respiratory tract.
Chemical
Mechanism:
Respiratory Chemoreceptors
If respiratory chemoreceptors were not functional, hypoxia would result;
no matter what happens, the subject would breathe at a normal, resting rate
1) Central Chemoreceptors are located on both sides of the medulla where
cranial nerves IX (glossopharyngeal nerves) and X (vagal nerves) leave the
brain. These chemoreceptors are primarily sensitive to pCO2 and the pH of blood. As pH falls (gets
more acidic) and pCO2 levels rise, these chemoreceptors provide stimulatory inputs to the
inspiratory center; this increases ventilation in an attempt to reduce H+ and CO2 in the blood. The chemoreceptors are
actually located in the interstitial space, outside of the blood-brain barrier.
As H+ions cannot diffuse through the blood-brain barrier, the
ability of decreased pH to stimulate respiration is due to H+ ions combining with bicarbonate ions
to form carbonic acid, which diffuses through the blood-brain barrier, some of
which dissociates to release H+ions in the interstitium.
In fact, the presence of carbon dioxide and H+ are so critical to
maintaining normal respiration, that if someone hyperventilates long enough,
they will reduce carbon dioxide so much that they may faint. This is
primarily because of the important role of carbon dioxide in maintaining
peripheral blood pressure. Carbon dioxide strongly stimulates constriction of
arterioles. When carbon dioxide levels drop with hyperventilation, blood
vessels relax, peripheral blood pressure falls, and less blood and oxygen are
delivered to the brain. If the level of oxygen in the brain falls low enough,
you pass out. A little bit different than passing out if you hold your
breath too long, in which case you just deplete oxygen in the blood. In
both cases, consciousness is lost because of lack of available oxygen for the
brain.
2) Remember that the dura mater, arachnoid and pia mater surround the
entire CNS, not just the spinal cord The Bone-Dura-Arachnoid-CSF space has a pH
of 7.32. This is just slightly more acidic than the pH of arterial (7.40) and
venous (7.38) blood. When the pCO2 is increased in the bloodstream, CO2 diffuses easily into the CSF space.
Chemoreceptors on the surface of the medulla sense this increase in CO2 in the CSF and this may be indirectly due
to the resultant decrease in pH. These chemoreceptors increase
respiratory rate to remove CO2 from the blood and eventually from the CSF by increasing ventilation.
The chemical
mechanism of the respiration is operated through the chemoreceptors.
Chemoreceptors:They are the
receptors which give response to change in the chemical constituents of blood
like..HypoxiaHypercapneaIncreased hydrogen ions concentration (decreased blood
pH)
Chemoreceptors
are classified into two groups:
Central chemoreceptors
Peripheral chemoreceptors
Central
chemoreceptors The chemoreceptors present in the brain are called
central chemoreceptors.
Situation: They
are situated in deeper part of medulla oblongata, close to the dorsal group of
neurons.This area is known as chemosensitivearea and neurons are called as
chemoreceptors.They are in
close contact with blood and CSF.
Action: They are very sensitive to increase in
hydrogen ion concentration. Hydrogen ion cannot cross the blood brain barrier
and blood cerebrospinal fluid barrier. On the other hand if carbon dioxide
increases in the blood as it is a gas it can cross both the barrier easily and
after entering the brain it combines with water to form carbonic acid.As
carbonic acid is unstable, it immediately dissociates into hydrogen and
bicarbonate ions. The hydrogen ion now stimulates the central cemoreceptors
which stimulates dorsal group of respiratory center (inspiratory group) and
increase rate and force of breathing.
Peripheral chemoreceptors:
Situation: The
receptors are present in peripheral portions of the body that’s why called as
peripheral chemoreceptors.
Action: They are
very sensitive to reduction in partial pressure of oxygen. Whenever, the
partial pressure of oxygen decreases these chemoreceptors become activated and
send impulses to inspiratory center and stimulate them. Thereby increases rate
and force of respiration and rectifies the lack of oxygen.
NEURAL CONTROL OF BREATHING
respiratory center - The series of paired and
functionally related autonomic nuclei located bilaterally in the reticular
formation of the brain stem; this control center consists of the medullary
rhythmicity area (containing the dorsal respiratory group (DRG) (formerly the
inspiratory area) and the ventral respiratory group (VRG) = (formerly the
expiratory area) and the pontine respiratory center (formerly the pneumotaxic
and the apneustic areas); these collections of neurons cooperate to regulate
the rate and depth of breathing as an involuntary unconscious activity in
response to the physiological needs of the body for O2 and CO2 exchange
and for blood acid-base balance.
medullary rhythmicity area - A collection of neurons in
the reticular formation within the medulla oblongata involved in establishing
or modifying the pattern for breathing; within this area are two key
components: (1) the ventral respiratory group (VRG) (formerly the
inspiratory area) which autorhythmically stimulates spontaneous ventilation,
resting or tidal breathing (eupnea), and (2) the dorsal respiratory group (DRG)
(formerly the expiratory area) which responds to situations beyond those of the
resting or tidal breathing (eupnea) to alter the pattern for ventilation in
response to the physiological needs of the body for O2 and CO2 exchange
and for blood acid-base balance.
dorsal respiratory group (DRG) (formerly
the inspiratory
area) - The collection of motor neurons forming nuclei within the
dorsal portion of the medullary rhythmicity area of the reticular formation
within the medulla oblongata which are involved in altering the pattern for
ventilation in response to the physiological needs of the body for O2 and
CO2 exchange and for blood acid-base balance; these neurons
stimulate neurons in the ventral respiratory group (VRG) to achieve those
effects; they are responsive to sensory information from chemoreceptors and
mechanoreceptors.
ventral respiratory group (VRG) (formerly the expiratory
area) - The collection of autorhythmic motor neurons forming nuclei
within the ventral portion of the medullary rhythmicity area of the reticular
formation within the medulla oblongata; this group contains both inspiratory
and expiratory neurons; the inspiratory neurons stimulate the diaphragm and
external intercostals for approximately 2 seconds to cause inspirations and
then the antagonistic expiratory neurons fire for approximately 3 seconds to
permit passive or stimulate active expirations; thereby inspiratory and
expiratory neurons cooperate in a negative feedback control relationship,
setting the basic rhythm of respiration (spontaneous ventilation, resting or
tidal breathing (eupnea)); VRG neurons may be influenced by the dorsal
respiratory group (DRG) for ventilations in situations other than eupnea.
pontine respiratory center (formerly
pneumotaxic and apneustic areas) - A collection of neurons in the reticular formation within the
pons which limit inspiratory duration by sending inhibitory signals to the
medullary rhythmicity area reducing duration of inspiratory impulses causing
shorter cycles which increases ventilation rate; these pontine respiratory
neurons receive input from higher brain centers and peripheral receptors, and
their output fine tunes the breathing rhythm during activities such as
speaking, sleeping, or exercising.
cortical influences - The action of higher,
"conscious" centers in the cerebral cortex which permit voluntary
control of ventilation by interacting with and over-riding the autonomic
centers in the medullary rhythmicity area; examples include the control of
ventilation during speech and singing, as well as deliberate forceful
inspirations, expirations, or attempts at breath holding; pain and certain
emotional states may also influence the rate and depth of ventilation in this
fashion.
Control Systems.
Spontaneous respiration is produced by rhythmic discharge of the motor neurons
that innervate the respiratory muscles. This discharge is totally dependent on
nerve impulses from the brain; breathing stops if the spinal cord is transected
above the origin of the premix nerves.
The pattern of motor stimuli during breathing can be
divided into inspiratory and expiratory phases. Inspiration shows a sudden,
ramped increase in motor discharge to the inspiratory muscles (including
pharyngeal dilator muscles). Before the end of inspiration, there is a decline
in motor discharge. Exhalation is usually silent, except at high minute ventilation rates.
The mechanism of generation of the ventilatory pattern is
not completely understood, but involves the integration of neural signals by
respiratory control centers in the medulla
and pons. The nuclei
known to be involved are divided into regions known as the following:
·
medulla (reticular formation)
o
ventral respiratory
group (nucleus retroambigualis, nucleus
ambigus, nucleus parambigualis and the pre-Bötzinger complex). The ventral
respiratory group controls voluntary forced exhalation and acts to increase the
force of inspiration.
o
dorsal respiratory
group (nucleus tractus solitarius). The dorsal
respiratory group controls mostly inspiratory movements and their timing.
·
pons
§
Coordinates transition between inhalation and exhalation
§
Sends inhibitory impulses to the
inspiratory area
§
The pneumotaxic center is involved
in fine tuning of respiration rate.
§
Coordinates transition between inhalation and exhalation
§
Sends stimulatory impulses to the inspiratory area – activates and prolongs
inhalate (long deep breaths)
§
overridden by pneumotaxic control from the apneustic area to end
inspiration
There is further integration in the anterior horn cells of the spinal cord.
Control of ventilatory pattern
Ventilation is normally controlled by the autonomic nervous system, with only
limited voluntary override. An exception to this is Ondine's
curse, where autonomic control is lost.
Two separate
neural mechanisms regulate respiration.
One is
responsible for voluntary control and the other for automatic control. The
voluntary system is located in the cerebral cortex and sends impulses to the
respiratory motor neurons via the corticospinal tracts. The automatic system is
located in the pons and medulla, and the motor outflow from this system to the
respiratory motor neurons is located in the lateral and ventral portions of the
spinal cord.
The motor
neurons to the expiratory muscles are inhibited when those supplying the
inspiratory muscles are active, and vice versa. These reciprocal innervations
are not due to spinal reflexes and in this regard differ from the reciprocal
innervations of the limb flexors and extensors. Instead, impulses in descending
pathways that excite agonists also inhibit antagonists, probably by
exciting inhibitory interneurons.
Medullary Centers.Rhythmic discharge of neurons in the
medulla oblongata produces automatic respiration. Respiratory neurons are of 2
types: those that discharge during inspiration (I neurons) and those that
discharge during expiration (E neurons). Many of these discharge at increasing
frequencies during inspiration, in the case of I neurons, or during expiration,
in the case of E neurons. Some discharge at decreasing frequencies, and some
discharge at the same high rate during inspiration or expiration. I neurons are
actively inhibited during expiration, E neurons during inspiration.
The area in the
medulla that is concerned with respiration has classically been called the
respiratory center, but there are actually 2 groups of respiratory neurons ).
The dorsal group of neurons near the nucleus of the tracts solitaries is the
source of rhythmic drive to the centra lateral premix motor neurons.
These neurons also project to and drive the ventral group. This group has 2
divisions. The cranial division is made up of neurons in the nucleus ambiguous
that innervate the ipsilateral accessory muscles of respiration, principally
via the vagus nerves. The caudal division is made up of neurons in the nucleus
retroambigualis that provide the inspiratory and expiratory drive to the motor
neurons supplying the intercostal muscles. The paths from these neurons to
expiratory motor neurons are crossed, but those to inspiratory motor neurons
are both crossed and uncrossed.
Pontine
& Vagal Influences. The rhythmic discharge of the neurons in the
respiratory center is spontaneous, but it is modified by centers in the pons
and by afferents in the vagus nerves from receptors in the lungs. The
interactions of these components can be analyzed by evaluating the results of
the experiments summarized diagrammatically in Fig .
Complete
transaction of the brain stem below the medulla
stops all respiration. When all of the cranial nerves (including the
vagi) are cut and the brain stem is transected above the pons regular breathing
continues. However, when an additional transaction is made in the inferior
portion of the pons , the inspiratory neurons discharge continuously and there
is a sustained contraction of the inspiratory muscles. This arrest of
respiration in inspiration is called apneusis. The area in the pons that
prevents apneusis is called the pneumotaxic center and is located in the
nucleus parabrachialis. The area in the caudal pons responsible for apneusis is
called the apneustic center.
Figure.
Respiratory neurons in the brain stem. Dorsal view of brain stem; cerebellum
removed. The effects of transecting the brain stem at various levels are also
shown. The spirometer tracing at the right indicate the depth and rate of
breathing, and the letters identify the level transaction. DRG, dorsal group of
respiratory neurons; VRG, ventral group of respiratory neurons; NPBL, nucleus
parabrachialis (pneumotaxic center); APC, apneustic center; 4th
vent, fourth ventricle; IC, inferior colliculus, CP, middle cerebellar
pedumcle. (Modified reproduced, with permission, from Mitchell R A, Berger A:
State of the art. Review of neural regulation of raspiration/ am. Rev Respir. Dis. 1975;111-206.)
When the brain
stem is transected in the inferior portion of the pons and the vagus nerves are
left intact, regular respiration continues. In an apneustic animal, stimulation
of the proximal stump of one of the cut vagi produces, after a moderate latent
period, a relatively prolonged inhibition of inspiratory neuron discharge.
There are stretch receptors in the lung parenchyma that relay to the medulla
via afferents in the vagi, and rapid inflation of the lung inhibits inspiratory
discharge (Hering-Breuer reflex). Thus, stretching of the lungs during
inspiration reflexly inhibits inspiratory drive, reinforcing the action of the
pneumotaxic center in producing intermittency of inspiratory neuron discharge.
This is why the depth of inspiration is increased after vagotomy in otherwise
intact experimental animals, although breathing continues as long as the
pneumotaxic center is intact.
When all pontine
tissue is separated from the medulla , respiration continues whether or not the
vagi are intact. This respiration is somewhat irregular and gasping, but it is
rhythmic. Its occurrence demonstrates that the respiratory center neurons are
capable of spontaneous rhythmic discharge.
The precise
physiologic role of the pontine respiratory areas is uncertain, but they
apparently make the rhythmic discharge of the medullary neurons smooth and
regular. It appears that there are topically discharging neurons in the
apneustic center which drive inspiratory neurons in the medulla, and these
neurons are intermittently inhibited by impulses in afferents from the
pneumotaxic center and vagal afferents.
REGULATION
OF RESPIRATORY CENTER ACTIVITY
Ventilatory
rate (minute volume) is tightly controlled and determined primarily by blood
levels of carbon dioxide as determined by metabolic
rate. Blood levels of oxygen become important in hypoxia. These levels are sensed by chemoreceptors
in the medulla oblongata for pH, and the carotid
and aortic
bodies for oxygen and carbon dioxide. Afferent neurons from the carotid bodies
and aortic bodies are via the glossopharyngeal nerve (CN IX) and the vagus nerve
(CN X), respectively.
Levels
of CO2 rise in the blood when the metabolic use of O2 is
increased beyond the capacity of the lungs to expel CO2. CO2
is stored largely in the blood as bicarbonate (HCO3-)
ions, by conversion first to carbonic acid (H2CO3), by
the enzyme carbonic anhydrase, and then by disassociation of this acid to H+
and HCO3-. Build-up of CO2 therefore causes an
equivalent build-up of the disassociated hydrogen ion, which, by definition,
decreases the pH of the blood.
During
moderate exercise,
ventilation increases in proportion to metabolic
production of carbon dioxide. During strenuous exercise, ventilation increases
more than needed to compensate for carbon dioxide production. Increased
glycolysis facilitates release of protons from ATP and metabolites lower pH and thus increase
breathing.
Mechanical
stimulation of the lungs can trigger certain reflexes as discovered in animal
studies. In humans, these seem to be more important in neonates and ventilated
patients, but of little relevance in health. The tone of respiratory muscle is
believed to be modulated by muscle
spindles via a reflex arc involving the spinal cord.
Drugs
can greatly influence the control of respiration. Opioids and
anaesthetic drugs tend to depress ventilation, especially with regards to carbon
dioxide response. Stimulants such as amphetamines
can cause hyperventilation.
Pregnancy
tends to increase ventilation (lowering plasma carbon dioxide tension below
normal values). This is due to increased progesterone
levels and results in enhanced gas exchange in the placenta.
Ventilation
is temporarily modified by voluntary acts and complex reflexes such as
sneezing, straining, burping, coughing and vomiting.
Receptors
play important roles in the regulation of respiration; central and peripheral chemoreceptors,
and mechanoreceptors.
·
Central chemoreceptors of the
central nervous system, located on the ventrolateral medullary surface, are
sensitive to the pH of
their environment.[1][2]
·
Peripheral chemoreceptors act
most importantly to detect variation of the oxygen in the arterial
blood, in addition to detecting arterial carbon dioxide and pH.
·
Mechanoreceptors are located in
the airways and parenchyma,
and are responsible for a variety of reflex responses. These include:
o
The Hering-Breuer reflex that terminates
inspiration to prevent over inflation of the lungs, and the reflex responses of
coughing, airway constriction, and hyperventilation.
o
The upper airway receptors are responsible for reflex responses such as, sneezing,
coughing, closure of glottis, and hiccups.
o
The spinal
cord reflex responses include the activation of additional respiratory
muscles as compensation, gasping response, hypoventilation, and an increase in
breathing frequency and volume.
o
The nasopulmonary and nasothoracic reflexes regulate
the mechanism of breathing through deepening the inhale. Triggered by the flow
of the air, the pressure of the air in the nose, and the quality
of the air, impulses from the nasal mucosa are transmitted by the trigeminal
nerve to the breathing centres in the brainstem,
and the generated response is transmitted to the bronchi, the intercostal muscles and the diaphragm.
In
addition to involuntary control of respiration by the respiratory center,
respiration can be affected by conditions such as emotional state, via input
from the limbic system, or temperature,
via the hypothalamus.
Voluntary control of respiration is provided via the cerebral
cortex, although chemoreceptor reflex is capable of overriding conscious
control.
A rise in the
P.CO2 or H+ concentration of arterial
blood or a drop in its P.O2 increases the level of respiratory neuron
activity, and changes in the opposite direction have a slight inhibitory
effect. The effects of variations in blood chemistry on ventilation are
mediated via respiratory chemoreceptors - receptor cells in the medulla and the
carotid and aortic bodies sensitive to changes in the chemistry of the blood
which initiate impulses that stimulate the respiratory center.
Superimposed on
this basic chemical control of respiration, other afferents provide nonchemical
controls for the fine adjustments that affect breathing in particular
situations held constant, the effects of excess in the blood are combated, and
the P.O2; is raised
when it falls to a potentially dangerous level. .
The respiratory
minute volume is proportionate to the metabolic rate, but the link between
metabolism and ventilation is CO2, not O2. The
receptors in the carotid and aortic bodies are stimulated by a rise in the P CO2
or H+ concentration of arterial blood or a decline in
its PO2. After denervation
of the carotid chemoreceptors, the response to a drop in PO2; is abolished; the predominant effect
of hypoxia after denervation of the carotid bodies is a direct
depression of the respiratory center.
Table. Stimuli
affecting the respiratory center
|
Chemical control |
|
|
CO2 |
Via CSF H+ concentration |
|
O2 |
Via carotid
and aortic bodies |
|
H+ |
|
|
Nonchemical control |
|
|
Afferents from proprioceptors |
|
|
Afferents from pharynx,
trachea, and bronchi for sneezing, coughing, and swolowing |
|
|
Vagal afferents from
inflation and deflation receptors |
|
|
Afferents from
baroreceptors: arterial, ventricular, pulmonary |
|
The response to
changes in arterial blood H+ concentration in the pH 7.3-7.5 range
is also abolished, although larger changes exert some effect. The response to
changes in arterial P.CO2 is affected only slightly; it is reduced
no more than 30-35%.
Carotid & Aortic
Bodies.There is a carotid body near the carotid bifurcation on each side, and
there are usually 2 or more aortic bodies near the arch of the aorta. Each
carotid and aortic body (glomus) contains islands of 2 types of cells, type I
and type II cells, surrounded by fenestrated
sinusoidal capillaries.
NONCHEMICAL
INFLUENCES ON RESPIRATION
Afferents from
"Higher Centers".
There are
afferents from the neocortex to the motor neurons innervating the respiratory
muscles, and even though breathing is not usually a conscious event, both
inspiration and expiration are under voluntary control. Pain and emotional
stimuli affect respiration, so there must also be afferents from the limbic
system and hypothalamus.
Since voluntary
and automatic control of respiration is separate, automatic control is
sometimes disrupted without loss of voluntary control. The clinical condition
that results has been called Ondine's curse. In German legend, Ondine was a
water nymph who had an unfaithful mortal lover. The king of the water nymphs
punished the lover by casting a curse upon him that took away all his automatic
functions. In this state, he could stay alive only by staying awake and
remembering to breathe. He eventually fell asleep from sheer exhaustion and his
respiration stopped. Patients with this intriguing condition generally have
disease processes that compress the medulla or bulbar poliomyelitis. The
condition has also been inadvertently produced in patients who have been
subjected to bilateral anterolateral cervical cordotomy for pain. This cuts the
pathways that bring about automatic respiration while leaving the voluntary
efferent pathways in the corticospinal and rubrospinal tracts intact.
Afferents from Proprioceptors. Carefully controlled experiments have shown
that active and passive movements of joints stimulate respiration, presumably
because impulses in afferent pathways from proprioceptors in muscles, tendons,
and joints stimulate the inspiratory neuron. This effect probably helps
increase ventilation during exercise.
Responses to Irritation
of the Air Passages. Sneezing and coughing are reflex responses to irritation
of receptors in the mucosa of the large respiratory passages. Irritation of the
walls of the trachea or large bronchi produces coughing, which begins with a
deep inspiration followed by forced expiration against a closed glottis. This
increases intrapleural pressure to
Other
Pulmonary Receptors. The vagally mediated inhibition of inspiration
produced by inflation of the lung has been mentioned above. The response is due
to stimulation of stretch receptors located in the smooth muscle of the
airways. Pulmonary deflation receptors that trigger inflation have also been
described, and the expiratory and inspiratory reflex responses to pulmonary
inflation and deflation, respectively, have been known as the Hering-Breuer
reflexes. However, the deflation receptors respond better to pulmonary
congestion and embolization, producing shallow, rapid breathing, and they have
come to be called J receptors instead, because of their juxtacapillary
location. There are also lung irritant receptors located between the epithelial
cells in the bronchi and bronchioles. When stimulated, they initiate
hyperventilation and bronchoconstriction, but their function in normal
breathing is not known.
Effect of Peripheral Stretch
Receptors (proprioceptors) on Respiration
When we exercise, we may experience an
increase in depth and rate of respiration to meet the increased oxygen
requirement. But the increase in respiration often precedes the actual increased
oxygen requirement There are
probably at least 2 components to this increase in respiration that precedes
the increased oxygen requirement. The first component is "anticipation of
exercise" and may involve activation of the sympathetic nervous system.
The second component involves activation of stretch receptors (proprioceptors)
in skeletal muscle and joints (tendon organs). Increased activity of stretch
receptors is detected by the medulla, and results in increased rate and depth
of respiration. The effect is very rapid, and shows an "added value"
to stretching before exercise (ie. in addition to heating up muscles and
connective tissues and reducing stretch-related injuries).
Impulses from
‘J’ receptors of lungs:
‘J’ receptors
are juxtacapillary receptors which are present in wall of the alveoli and have
close contact with the pulmonary capillaries.These receptors get stimulated
during conditions like pulmonary edema, pulmonary congestion, pneumonia as well as due to
exposure of exogenous and endogenous chemicals like histamine,
serotonin.Stimulation of ‘J’ receptor produces a reflex response called apnea.
Impulses from irritant receptors of lungs:
Irritant
receptors are situated on the wall of bronchi and bronchioles of lungs.They got
stimulated by harmful chemicals like ammonia and sulfur dioxide. Stimulation of
irritant receptors produces reflex hyperventilation along with bronchospasm
which prevents entry of harmful chemicals into the alveoli.
Impulses from
Proprioceptors: Proprioceptors are the receptors which give
response to the change in the position of different parts of the body.This
receptors are situated in joints, muscles and tendons. They get stimulated
during exercise and sends impulses to the cerebral cortex.Cerebral cortex in
turn by activating medullary respiratory centres causes hyperventilation.
Respiratory
Components of Other Visceral Reflexes.
The respiratory
adjustments during vomiting, swallowing and gagging; inhibition of respiration
and closure of the glottis during these activities not only prevent the
aspiration of food or vomitus into the trachea but, in the case of
vomiting, fix the chest so that contraction of the abdominal muscles increases
the intra-abdominal pressure. Similar glottis closure and inhibition of
respiration occur during voluntary and involuntary straining.
Hiccup is a
spasmodic contraction of the diaphragm that produces an inspiration during
which the glottis suddenly closes. The glottis closure is responsible for the
characteristic sensation and sound. Yawning is a peculiar
"infectious" respiratory act the physiologic basis and significance
of which are uncertain. However, under ventilated alveoli have a tendency to
collapse, and it has been suggested that the deep inspiration and stretching
open them alveoli and prevent the development of atelectasis. Yawning also
increases venous return to the heart.
Respiratory
Effects of Baroreceptor Stimulation. Afferent fibers from the baroreceptors
in the carotid sinuses, aortic arch, atria, and ventricles relay to the
respiratory center as well as the vasomotor and cardioinhibitory centers in the
medulla. Impulses in them inhibit respiration, but the inhibitory effect is
slight and of little physiologic importance. The hyperventilation in shock is
due to chemoreceptor stimulation caused by acidosis and hypoxia secondary to
local stagnation of blood flow and is not baroreceptor mediated. The activity
of the inspiratory neurons affects the blood pressure and heart rate and
activity in the vasomotor center and the cardiac centers in the medulla may
have minor effects on respiration.
Airway
receptors. that
may have some relevance to the effect of anesthetics include laryngeal and
pulmonary irritant receptors and pulmonary stretch receptors. These receptors
play an important role in the regulation of breathing patterns, laryngeal and
pulmonary defense mechanisms, and bronchomotor tone. Irritant receptors are
situated between airway epithelial cells and may mediate rapid reflex responses
such as coughing, laryngospasm, bronchoconstriction, and mucus secretion
following the induction of general anesthesia, abrupt increases in the inspired
concentration of volatile anesthetics, and sudden mechanical deformation of the
laryngotracheobronchial system.
Slow-adapting pulmonary stretch receptors, located
within small airway smooth muscle (high concentration near the carina), respond
to stretching or changes in lung volume. Increases in lung volume increase
afferent nerve traffic via the vagus nerve to the respiratory control center, thereby
inhibiting further inspiration (the Hering-Breuer reflex). This limitation of
inspiration elicited by pulmonary stretch receptors may determine the
relationship between tidal volume and respiratory frequency, but unlike in
animals, the Hering-Breuer reflex cannot be demonstrated in the awake resting
human during normal tidal volume breathing. The alteration in ventilatory
pattern by anesthetics has been attributed to sensitization of pulmonary
stretch receptors, leading to lower tidal volumes and tachypnea. The presence
of volatile anesthetics increased vagal afferent discharge at varying lung
volumes in decerebrate cats (i.e., sensitization of pulmonary stretch
receptors), but little evidence exists of such a mechanism in humans. There is
evidence in the cat that halothane-induced tachypnea is primarily a
suprapontine effect, but the mechanism of production of tachypnea with
decreased tidal volume in anesthetized humans remains unclear.
The direct effects of halothane, isoflurane, and
enflurane on pulmonary and laryngeal irritant receptors and on tracheobronchial
slow-adapting stretch receptors have been investigated in spontaneously
breathing and vagotomized, paralyzed dogs. All three volatile anesthetics
increase the activity of laryngeal irritant receptors and inhibit pulmonary
irritant receptors. In addition, the volatile anesthetics elevate the
excitation threshold and increase the sensitivity of low-threshold stretch
receptors. The inspiratory activity was augmented while the end-expiratory activity
was greatly attenuated. The clinical implications of these findings have yet to
be determined, but these anesthetic-induced changes may in part relate to
effects on reducing bronchomotor tone.
It has been suggested that general anesthesia may
result in posterior tongue displacement, producing upper airway obstruction;
however, several recent studies do not confirm this. Anteroposterior
displacement of upper airway structures occurs with changes in head position
that are in the same direction as that of the mandible. In addition, general
anesthesia and paralysis may widen the dimensions of the larynx, but the
nasopharyngeal airway decreases in size. Volatile anesthetics produce a greater
depression of the upper airway electromyogram or nerve activity as compared to
that of the diaphragm in intact anesthetized, spontaneously breathing cats and
in paralyzed, ventilated, vagotomized cats. The extent to which this depression
of upper airway motoneuron activity is a result of an anesthetic-induced
inhibition of the reticular activating system is unknown.
The epithelium of the trachea, bronchi, and
bronchioles is supplied with sensory nerve endings that are stimulated by
irritants that enter the respiratory airways. These cause coughing and
sneezing. They possibly also cause bronchial constriction in such diseases as
asthma and emphysema.
Function of Lung
"J" Receptors. A few sensory nerve endings occur in the alveolar
walls in Juxtaposition to the pulmonary capillaries, from whence comes the name
"J" receptors. They are stimulated when irritant chemicals are
injected into the pulmonary blood, and they are also excited when the pulmonary
capillaries become engorged with blood or when pulmonary edema occurs in such
conditions as congestive heart failure. Though the functional role of the J
receptors is not known, their excitation perhaps does give the person a feeling
of dyspnea.
Limitation of
Inspiration by Lung Inflation Signals - the
Hering-Breuer Inflation Reflex
This is a
reflex triggered to prevent over-inflation of the lungs. Pulmonary stretch
receptors present in the smooth muscle of the airways respond to excessive
stretching of the lung during large inspirations.
Once
activated, they send action potentials through large myelinated fibers of the
paired vagus nerves to the inspiratory area in the medulla and apneustic area
of the pons. In response, the inspiratory area is inhibited directly and the
apneustic area is inhibited from activating the inspiratory area. This inhibits
inspiration, allowing expiration to occur.
The
Hering–Breuer inflation reflex ought not
be confused with the deflation reflex discovered by the same individuals,
Hering and Breuer. The majority of this page discusses the inflation reflex;
the deflation reflex is considered separately at the end.
The Hering–Breuer inflation reflex, named for Josef
Breuer and Ewald Hering, is a reflex triggered to
prevent over-inflation of the lungs. Pulmonary stretch receptors present in
the smooth muscle of the airways respond to excessive stretching of the lung
during large inspirations.
Once activated, they send action
potentials through large myelinated fibers[4]
of the paired vagus nerves to the inspiratory area in the medulla and
apneustic
center of the pons.
In response, the inspiratory area is inhibited directly and the apneustic
center is inhibited from activating the inspiratory area. This inhibits
inspiration, allowing expiration to occur.
The Hering–Breuer inflation reflex ought not be confused with the deflation
reflex discovered by the same individuals, Hering and Breuer. The majority of
this page discusses the inflation reflex; the deflation reflex is
considered separately at the end.
Located in the
walls of the bronchi and bronchioles throughout the lungs are stretch receptors
that transmit signals through the vagi into the dorsal respiratory group of
neurons when the lungs become overstretched. These signals affect inspiration
in much the same way as signals from the pneumotaxic center; that is, they
limit the duration of inspiration .
Therefore, when the lungs become overly
inflated, the stretch receptors activate an appropriate feedback response that
"switches off" the inspiratory ramp and thus limits further
inspiration. This is called the Hering-Breuer inflation reflex. This reflex
also increases the rate of respiration because of the reduced period of inspiration,
the same as is true for signals from the pneumotoxic center.
Figure 3. Effect
of vagal stimulation (between arrows) on discharge rate in phrenic nerve fibers
in an “isolated inspiratory center preparation.” The cat had been prepared by
cutting both vagi and transecting the medulla at the caudal border of the pons,
this cutting off the pneumotaxic center. In A, the continuous discharge of the
inspiratory neurons is shown. In B and C, stimulation of the proximal stump of
one vagus produces, after a considerable latent period, inhibition of
inspiratory discharge. The animal exhales when the inspiratory discharge stops,
as is shown by the record of respiratory excursions (upper line in B and C;
inspiration upward).
However, in
human beings, the Hering-Breuer reflex probably is not activated until the
tidal volume increases to greater than approximately
EFFECTS OF EXERCISE
We breathe oxygen
into the body from the atmosphere. While this oxygen does not itself contain
useable energy, it is the key that unlocks the energy stored in
previously-ingested food. As the energy demands of the contracting muscles
change during exercise, so must their energy and oxygen provision. But oxygen
comprises only 21% of the atmospheric air; one therefore needs to inhale a
volume of air each minute which is at least five times the volume of oxygen
which is being absorbed out of the lungs by the body.
Lung ventilation — the volume breathed in and out per
minute — however, is not five times that of the rate of oxygen utilization
for metabolism, rather, it is twenty-five times. This is because most of
the oxygen is breathed back into the atmosphere during expiration: only 20% or
so of the inspired oxygen is actually taken up by the blood coursing through
the lungs en route to the cells.
The air taken into the lungs does not all reach the
gas-exchange regions (the alveoli).
Airways that conduct air to the alveoli do not themselves take part in this
exchange: only the volume of air that gets beyond this dead space into
the alveoli contributes to the gas exchange. Consequently the alveolar
ventilation is less than the total ventilation — and this is the volume
which provides the oxygen to be taken up into the body.
The alveolar oxygen concentration, and its equivalent
oxygen pressure, is determined by the balance between the supply of oxygen to
the alveoli and the demand for its uptake into the blood: the alveolar
ventilation per minute and the oxygen consumption per minute. The alveolar
oxygen pressure in turn establishes the oxygen pressure in the arterial blood,
which is normally maintained at, or close to, a constant level during exercise,
the same level as when at rest, despite the body's oxygen consumption
increasing more than 10-fold. This can only be achieved if the alveolar
ventilation increases proportionally. Normally it does so, increasing so that
it maintains a ratio of about twenty times the oxygen uptake rate, for moderate
exercise, with the ratio for total ventilation being about twenty five.
While this characterizes the ventilation needed to
maintain the level of oxygen in the arterial oxygen, it may or may not be
appropriate for the other vital breathing requirement during exercise — the
defence of blood and tissue acidity.
The exercise-induced challenge to the body's acidity
levels has two different origins. Firstly, foodstuffs that serve as energy
sources for exercise (carbohydrates
and fats) are composed entirely of hydrogen,
carbon, and oxygen atoms. During the progressive metabolic fragmentation of
food molecules, hydrogen atoms are stripped away, to link with oxygen, yielding
energy.
For example, for glucose:
C6H
12O6 + 6O2 → 6H2O + 6CO2
This leaves
the carbon and oxygen to be vented into the atmosphere as carbon dioxide.
As the body's carbon dioxide production from this source is normally
approximately equal to its oxygen consumption during exercise, the same level
of ventilation can serve both purposes: intake and exhaust. However, if
ventilation does not increase sufficiently during exercise, the oxygen level
will fall in the blood and tissues, and the carbon dioxide level will rise.
Such an increase in carbon dioxide would increase blood and tissue acidity.
The body's
acidity is determined by the concentration of hydrogen ions [H+] —
the positively-charged protons which form the nuclei of the smallest of all
atoms. An increase in carbon dioxide in body fluids increases the concentration
of [H+]. For [H+] to be stabilized in the arterial blood
leaving the lungs, the carbon dioxide level needs to be regulated by exhaling
the carbon dioxide at a rate equivalent to its production rate
Normally, for
moderate exercise, ventilation does indeed increase in proportion to the
increased metabolic rate, thereby maintaining arterial blood levels of both
oxygen and carbon dioxide (and hence [H+]) at, or close to, resting
levels. This control is mediated through an interaction of neural and
blood-borne mechanisms. The neural mechanisms which lead to muscle contraction
also simultaneously signal the breathing control centres of the brain; these
receive neural information from the contracting muscles as well. If the
resulting drive to breathe is not appropriate, then an ‘error’ in the arterial
oxygen, carbon dioxide, and [H+] levels is sensed by chemoreceptors
which ‘sample’ the blood in the carotid arteries perfusing the brain. This
provides the ‘fine tuning’ of the control system.The second challenge to
arterial [H+] stability occurs only at higher work rates, where the
energy demands cannot be met entirely through aerobic (i.e. oxygen-linked)
metabolism. At these work rates the aerobic transfer of energy is supplemented
by degradation of carbohydrates to lactic acid — present in the form of a
lactate ion [L-] and [H+]. This component is anaerobic
metabolism (it utilizes no oxygen). The fitter the subject, the higher the
work rate at which it begins to contribute (see figure). The resulting increase
in [H+] has a number of deleterious effects on exercise tolerance:
impaired muscle contraction; perception of limb fatigue; and ‘shortness of
breath’.
As exercise
continues at this high intensity, the body's acidity level can only be
maintained (or its increase constrained) if the carbon dioxide-related
component of the acidity is reduced. The body therefore ‘compensates’ by
increasing ventilation proportionally more relative to carbon dioxide
production. This reduces alveolar and arterial carbon dioxide levels (see
figure) as a result of the increased carbon dioxide ‘washout’. Clearly, the
greater the amount of carbon dioxide ‘washed out’ under these conditions, the
less will be the increase in acidity for any
References:
1. Review of Medical Physiology // W.F.Ganong. – 24th
edition, 2012.
2. Textbook of Medical Physiology //
A.C.Guyton, J.E.Hall. – Eleventh edition, 2005.
3.
The human organs by R.M.DeCoursey, NMcGraw-Hill book company.