1. BIOMECHANICS OF
RESPIRATORY ACT.
2. VENTILATION
OF LUNGS. TRANSPORT
OF GASES
3. Regulation
of breathing
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.
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 |
TRANSPORT OF GASES.
Gas exchange in the lungs occurs across an estimated
300 million tiny (0.25 to
cells fuse with those of type I alveolar cells, the
diffusion distance can be as small as 0.3 μm , which is about 1/100th the width of a human hair.
Alveoli are polyhedral in shape and are usually clustered, like the units of a
honeycomb. Air within one member of a cluster can enter other members through
tiny pores . These clusters of alveoli usually occur at the ends of respiratory
bronchioles, the very thin air tubes that end blindly in alveolar sacs.
Individual alveoli also occur as separate outpouchings along the length of
respiratory bronchioles. Although the distance between each respiratory
bronchiole and its terminal alveoli is only about
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.
Unlike
liquids, gases expand to fill the volume available to them, and the volume
occupied by a given number of gas molecules at a given temperature and pressure
is (ideally) the same regardless of the composition of the gas.
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.
Gas diffuses from areas of high pressure to area of low pressure, the rate of diffusion depending upon the concentration gradient and the nature of the barrier: between the 2 areas. When a mixture of gases is in contact with and permitted to equilibrate with a liquid each gas in the mixture dissolves in the liquid to an extent determined by its partial pressure and its solubility in the fluid. The partial pressure of a gas in a liquid is that pressure which in the gaseous phase in equilibrium with the liquid would produce the concentration of gas molecules found in the liquid.
GAS EXCHANGE IN THE LUNG
Composition
of Alveolar Air. Oxygen continuously diffuses out of the gas in the alveoli
(alveolar gas) into the bloodstream, and C02 continuously diffuses
into the alveoli from the blood. In the steady state, inspired air mixes with
the alveolar gas, replacing the O2 that has entered the blood
and diluting the CO2 that has entered the alveoli. Part of this
mixture is expired. The O2 content of the alveolar gas then
falls and its CO2 content rises until the next inspiration. Since
the volume of gas in the alveoli is about
Sampling Alveolar Air . Theoretically, all but the first 150
ml expired with each expiration is alveolar air, but there is always some
mixing at the interface between the dead space gas and the alveolar air. A
later portion of expired air is therefore the portion taken for analysis. Using
modern apparatus with a suitable automatic valve, it is possible to collect the
last 10 ml expired during quiet breathing. The composition of alveolar gas is
compared with that of inspired and expired air.
Diffusion Capacity. Partial Pressures of O2 and CO2
in the body (normal, resting conditions): Alveoli: P.O2 =
Alveolar
capillaries
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 =
Blood leaving the alveolar capillaries returns
to the left atrium & is pumped by the left ventricle into the systemic
circulation. This blood travels through arteries & arterioles and into the
systemic, or body, capillaries. As blood travels through arteries &
arterioles, no gas exchange occurs.
Entering
the systemic capillaries
§
PO2 =
§
PCO2 =
Body cells (resting conditions)
§
PO2 =
§
PCO2 =
Because of the differences in
partial pressures of oxygen & carbon dioxide in the systemic capillaries
& the body cells, oxygen diffuses from the blood & into the cells,
while carbon dioxide diffuses from the cells into the blood.
Leaving the systemic capillaries
§
PO2 =
§
PCO2 =
Blood leaving the systemic
capillaries returns to the heart (right atrium) via venules & veins (and no
gas exchange occurs while blood is in venules & veins). This blood is then
pumped to the lungs (and the alveolar capillaries) by the right ventricle.
Figure. Partial pressure and diffusion at the respiratory membrane.
While in
the alveolar capillaries, the diffusion of gasses occurs: oxygen diffuses from
the alveoli into the blood and carbon dioxide from the blood into the alveoli.
Leaving the alveolar capillaries: PO2 =
Blood
leaving the alveolar capillaries returns to the left atrium and is pumped by
the left ventricle into the systemic circulation. This blood travels through
arteries & arterioles and into the systemic, or body, capillaries. As blood
travels through arteries & arterioles, no gas exchange occurs.
Entering
the systemic capillaries: PO2 =
Body
cells (resting conditions): PO2 =
Oxygen
moves from the alveoli to the red blood cells along the short path. The PO2
of alveolar air is
There is
no evidence that any process other than passive diffusion is involved in the
movement of O2; into the blood along this pressure gradient. O2
dissolves in the plasma and enters the red blood cells, where it combines with
hemoglobin. Diffusion into the blood must be very rapid, since the time for
each milliliter of blood is in the capillaries is short. Nevertheless, O2
diffusion is adequate in health to raise the PO2; of the blood to
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.
Figure .
Summary of PO2 and PCO2
values in air, lungs, blood, and tissues, graphed to emphasize the fact that
both O2 and CO2 diffuse "downhill" along
gradients of decreasing partial pressure.
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 (Table ).
Table .
Gas content of blood.
|
Gas |
Ml/dl
of blood containing |
|||
|
Arterial
blood (PO2
|
Venous
blood (PO2
|
|||
|
Dissolved |
Combined |
Dissolved |
Combined |
|
|
O2 |
0.23 |
19.5 |
0.12 |
15.1 |
|
CO2 |
2.62 |
46.4 |
2.98 |
49.7 |
|
N2 |
0.96 |
0 |
0.98 |
0 |
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.
OXYGEN TRANSPORT
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
Hemoglobin & Oxygen.
The
dynamics of the reaction of hemoglobin with O2 make it a
particularly suitable O2 carrier. Hemoglobin is a protein made up of
4 subunits, each of which contains a hem moiety attached to a polypeptide
chain. Hem is a complex made up of porphyry and 1 atom of ferrous iron. Each of
the 4 iron atoms can bind reversibly one O2 molecule. The iron stays
in the ferrous state, so that the reaction is an oxygenation, not an oxidation.
When hemoglobin takes up a small amount of O2, the R state is
favored and additional uptake of O2 is facilitated. This is why the
oxygen hemoglobin dissociation curve, the curve relating percentage saturation
of the O2-carrying power of hemoglobin to the P.O2,
has a characteristic sigmoid shape. Combination of the first hem in the Hb
molecule with O2 increases the affinity of the second hem for O2,
and oxygenation of the second increases the affinity of the third, etc, so that
the affinity of Hb for the fourth O2 molecule is many times that for
the first. When hemoglobin takes up O2, the 2/3 chains move closer
together; when O2 is given up, they move further apart. This
shift is essential for the shift in affinity for O2 to occur. When
blood is equilibrated with 100% O2 (P.O2 =
Thus, at rest the tissues remove about 4.6 ml of O2
from each deciliter of blood passing through them (Table 44-4); 0.17 ml of this
total represents O2 that was in solution in the blood, and
the remainder represents O2 that was liberated from hemoglobin. In
this way, 250 ml of O2 per minute is transported from the blood to
the tissues at rest.
Figure.
Oxygen hemoglobin dissociation curve pH 7,40. temperature 380.
Factors
Affecting the Affinity of Hemoglobin for Oxygen. Three important conditions
affect the oxygen hemoglobin dissociation curve: the pH, the temperature, and
the concentration of 2,3-diphosphoglycerate (DPG; 2,3-DPG). A rise in
temperature or a fall in pH shifts the curve to the right .
When the
curve is shifted in this direction, a higher P.O2; is
required for hemoglobin to bind a given amount of O2. Conversely, a
fall in temperature or a rise in pH shifts the curve to the left, and a lower P O2 is required to bind a given amount of
O2. A convenient index of such shifts is the P50,
the P O2 at which the hemoglobin is half
saturated with O2; the higher the P50, the lower
the affinity of hemoglobin for O2.
Figure.
Effect temperature and pH on hemoglobin dissociation curve.
The
decrease in O2 affinity of hemoglobin when the pH of blood falls is
called the Bohr effect and is closely related to the fact that deoxyhemoglobin
binds H+ more actively than does oxyhemoglobin.
The pH of
blood falls as its CO2 content increases , so that when the PCO2
rises, the curve shifts to the right and the P50 rises.
Most of the unsaturation of hemoglobin that occurs in the tissues is secondary
to the decline in the P O2, but
an extra 1-2% unsaturation is due to the rise in P.CO2 and
consequent shift of the dissociation curve to the right.
2,3-DPG
is very plentiful in red cells. It is formed from 3-phosphoglyceraldehyde,
which is a product of glycolysis via the Embden-Meyerhof pathway. It is a highly
charged anion that binds to the Beta chains of deoxygenated hemoglobin
but not to those of oxyhemoglobin. One mole of deoxygenated hemoglobin
binds 1 mole of 2,3-DPG. In effect:
HbO2
+ 2,3-DPG =Hb-2,3-DPG + O2
In this
equilibrium, an increase in the concentration of 2,3-DPG shifts the reaction to
the right, causing more O2 to be liberated. ATP binds to
deoxygenated hemoglobin to a lesser extent, and some other organic phosphates
bind to a minor degree.
Factors
affecting the concentration of 2,3-DPG in the red cells include pH. Because
acidosis inhibits red cell glycolysis, the 2,3-DPG concentration falls when the
pH is low. Thyroid hormones, growth hormone, and androgens increase the
concentration of 2,3-DPG and the P50.
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.
Figure .
Dissociation curve of hemoglobin and myoglobin at 380, pH 7,40.
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.
Carbon dioxide - transported from the body
cells back to the lungs as:
1 - bicarbonate (HCO3) - 60%
formed when CO2 (released by cells
making ATP) combines with H2O (due to the enzyme in red blood cells called
carbonic anhydrase) as shown in the diagram below
2 - carbaminohemoglobin - 30%
formed when CO2 combines with
hemoglobin (hemoglobin molecules that have given up their oxygen)
3 - dissolved in the plasma - 10%
The resultant
carbon dioxide, which is produced from metabolism and given out by the tissue,
is passed into blood through the tissue fluid and conveyed back to the
respiratory surfaces along with the blood stream. But by plasma
and hemoglobin of blood. Blood transports carbon dioxide in three ways, namely:
(1) As
carbonic acid
(2) As
bicarbonates of sodium and potassium and
(3) As
carbominohemoglobin
All these
compounds are reversible compounds. About 10% of total carbon dioxide is
carried by the blood in the dissolved state as carbonic acid (CO2 +
H2O – H2CO3) but 80% of CO2 as Sodium bicarbonate in the plasma
and as potassium bicarbonate in the plasma and as potassium bicarbonate in the
corpuscles and the remaining 10% as carbamino-hemoglobin (a loose compound
formed by CO2 + hemoglobin).
Now the
question is if they are conveyed in compound from but not in
Therefore,
the carbon dioxide so formed is removed by diffusion before the blood leaves
the lung. This transportation of gases also comes under external respiration.
In
short: from tissue – diffuses into – tissue
(CO2 high
concentration)
From tissue
fluid – diffuses into – blood
(Free CO2)
(i) By
blood plasma:
As physical
solution:
10% CO2+ H2O – Carbonic
anhydrase – H2CO3
(Carbon
dioxide) (Water) enzyme (carbonic acid)
(ii) By
R. B. C. Hemoglobin as Carbamino Compounds:
10% carbon
dioxide + hemoglobin – carbamino hemoglobin
(iii)
As Bicarbonate compounds:80% carbon dioxide – in plasma as
sodium bicarbonate
2Na HCO3– Na2CO3+ H2O + CO2
(Sodium
bicarbonate)
In corpuscles
as potassium bicarbonate i.e. - 2 K. H.
(Potassium
bicarbonate)
CO3– K2CO2+ H2O + CO3
Release
of CO2 at the Respiratory Surface:
Carbonic
acid, bicarbonates of sodium and potassium and carbamino compounds are carried
to the lungs where they breakdown under the influence of various factors and
liberate free CO2.
Measuring of thorax sizes in different phases
of breathing
1)
Measure the sizes of thorax by
means of tape-measure. Put it under the angles of scapulae and on the level of
thoracic papilla. Measure:
a)
During the deep inhalation;
b)
During the deep exhalation.
Define
the excursion of thorax (the difference between the sizes measured during the
inhalation and exhalation).
Write
down the results in to the table:
|
# |
Sizes of
thorax |
Excursion of
thorax |
|
|
During the deep inhalation |
During the deep exhalation |
||
|
1 |
|
|
|
2)
Legs of compasses put the inferior margins of ribs arcs on the same level, as
in the previous measuring (by means of metallic compasses). Define the changes
of sizes of thorax in the frontal ltness during the deep inhalation and deep
exhalation. Legs of compasses put to the inferior margin of breast bone and on
the same level to the spine. Define the excursion of thorax in sagittal
flatness during the deep inhalation and deep exhalation.
Write
down the results in to the table:
|
# |
Frontal flatness |
Sagittal
flatness |
||||
|
inhalation |
exhalation |
excursion |
inhalation |
xhalation |
excursion |
|
|
1 |
|
|
|
|
|
|
|
2 |
|
|
|
|
|
|
|
3 |
|
|
|
|
|
|
In
conclusion define whether the excursion of thorax corresponds to the
physiologic norm; explain the mechanism of size changing of thorax in different
phases of breathing.
Changes of pressure in pleural cavity and lungs
during the modeled breathing
To
demonstrate the changes that appeared in the thoracic cavity during the
breathing use the model of Donders. Determine the pressure in the “ pleural
cavity” and lungs during the inhalation and exhalation. Pay attention to the
volume of lungs when the position of diaphragm is changed. Show graphically
changes of lungs volume, pressure in lungs and pleural cavity in different
phases of breathing.
In
conclusion define the mechanism of pressure changes in “pleural cavity” and
lungs during the modeled breathing.
Measuring of pressure in respiratory ways
Fix
the narcotized rat on the table. Make a clit on the middle cervical line till
the trachea. Introduce there an injective needle connected manometer. Register
changes of pressure in respiratory ways during the inhalation and exhalation
and show the results graphically.
In
conclusion define whether the results correspond to the physiologic regularity
changes of pressure in respiratory ways while breathing.
Spirometry
By dry spirometer
Put closely the desinfected glass tube on the
input tube of the spirometer. Turning the cap, put the scale of the set in such
a way that the arrow is in zero position. Breathing out into the spirometer tube, determine the
respiratory volume, reserve volume of breath out and
life capacity of the lungs.
The results must be given in the following way:
|
No. |
Respiratory volume |
Reserve volume of breath out |
Life capacity |
|
1. 2. 3.. |
|
|
|
|
M |
|
|
|
Spirography
The examinee should take into his mouth
desinfected tube connected with the system of spirograph. Put the forceps on his nose. Then write
the spirogram. Determine the
breath frequency according to the time mark (interval between the waves is
equal to 5 seconds), breath volume, reserve volume of breath in and breath out
(
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 centersPontine centers
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 stretch receptors of lung.
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.
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:
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.[citation needed]
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 2.
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.
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
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.