EXCHANGES WITH THE ENVIRONMENT

RESPIRATION
 Aerobic metabolism in animal cells needs oxygen. The end products, carbon
dioxide (and water), must be removed from the body. This exchange of gases
is called respiration (Respiration is the process by which living organisms
take in oxygen and release carbon dioxide).
 Respiration can be considered at three levels: (i) External Respiration (at the
whole organism level): gas exchange between the environment and specialized
respiratory organs. (ii) Internal Respiration: gas exchange between body
fluids and cells. (iii) Cellular Respiration: the use of oxygen within the cells.
In most cells, cellular respiration is accomplished in four stages, divided
between anaerobic and aerobic series of reactions.
 Besides obtaining sufficient quantity of oxygen and eliminating carbon
dioxide formed in the body, respiration serves the following purposes: it helps
(i) in keeping the functions of the blood normal by adjusting changes in the pH
of the blood, (ii) in maintaining proper oxygen tension of the blood, and (iii) in
maintaining normal body temperature.
Requirements for Gas Exchange
 Gas exchange (external respiration) needs moist gas-permeable membranes,
high oxygen tension in water or air, and a high carbon dioxide tension in the
body fluids.
 Gas exchange through the body surface directly to the tissues is only feasible
for small organisms. Simple diffusion is possible through a moist external
surface to the transport system (blood), for example in the earthworm.
 A number of organisms like protozoans, coelenterates and flatworms do not
have specialized respiratory organs and as such the gases enter and leave the
body by the process of slow diffusion. Simple diffusion is limited by body
size; only a spherical or thread-like animal with a radius of less than 1 mm can
use simple diffusion.

Gas Exchange in Humans

 In humans, gas exchange takes place within the two lungs contained within
the thoracic cavity. Surrounding the elastic lungs are two thin membranes, the

1
 pleura, which secrete a lubricating fluid. (Each lung is enclosed in a
membranous sac, or pleura. There are two layers of pleura: Parietal pleura.
This is the outer membrane, which is attached to the inside of the chest wall,
and the superior surface of the diaphragm. Visceral pleura: This is the inner
membrane, which is attached to the outer surface of the lung. The pleurae are
composed of serous membrane which secretes fluid into the potential space,
the pleural cavity, between the parietal and visceral layers. This fluid provides
lubrication for the movement which takes place during respiration).
 Inspiration (breathing in) and expiration (breathing out) usually take place
through the nose.
 The nasal cavities are lined with hairs and cilia which trap dust; the nasal
epithelium secretes mucus which also collects debris and humidifies the air;
the cavities have a rich blood supply which keeps the temperature high and
warms the air.

2
  Air then passes to the pharynx and thence to the larynx, a triangular box
across which are stretched the two ligamentous vocal cords. The air then
passes down the trachea (wind-pipe), a long tube lined with ciliated
epithelium and reinforced with cartilaginous C-rings (to prevent its collapse as
food is passed down the adjacent esophagus). The trachea branches into the
two bronchi which subdivide into smaller and smaller air-tracts, the
bronchioles. These are lined with smooth muscle whose contraction adjusts
resistance to air-flow. Cilia lining the tracts waft debris back up to the
pharynx.
 Gas exchange occurs within alveoli, small air-sacs clustered around the ends
of the bronchioles. Each alveolus is about 0.1–0.2 mm in diameter and is
surrounded by blood capillaries. The alveoli and capillary walls are each one
cell thick, separated by thin basement membranes: thus the distance between
the air in the alveolus and the blood in the capillary is only about 0.5 μm. Gas
is exchanged by diffusion. Human lungs have about 300 million alveoli with a
surface area of about 70m2, about 40 times the surface area of the body.
 Thus the getting of gas to and from the alveoli is termed ventilation.
Ventilation is measured as the volume of gas that is inspired or expired in a
unit of time. Blood passing through the pulmonary capillary bed removes O2
from the alveolar air and adds CO2. Ventilation of the alveoli, on the other
hand, adds O2 to the alveolar air and removes CO2.

Respiratory Mechanism and Lung Volumes

3
1. Respiratory Mechanism:
 The lungs and the chest wall are elastic structures.
 Air flows in and out of the lungs when the air pressure is greater or less than
external atmospheric pressure. The pressure in the lungs is varied by changes
in the volume of the thorax effected by contraction and relaxation of the
muscular diaphragm at the base of the thorax (contraction of the diaphragm
lowers it and so increases thorax volume); contraction of intercostal muscles
swings up the rib-cage to increase the thoracic cavity volume further; the intra-
pleural pressure at the base of the lungs at the start of inspiration, decreases;
the lungs are pulled in to a more expanded position, the pressure in the air
way becomes slightly negative, and air flows in to the lungs.
 At the end of inspiration, the lung recoil begins to pull the chest back to the
expiratory position. The pressure in the airway becomes slightly positive, and
air flows out of the lungs. Expiration during quiet breathing is passive in the
sense that no muscles which decrease intra-thoracic volume contract.
However, there is some contraction of inspiratory muscles in the early part of
expiration; this contraction exerts a braking action on the recoil forces and
slows expiration.
 (In newborn babies, the ribs are at right angles to the vertebral column, so
breathing is wholly diaphragmatic).
Muscle Contraction Diagram

4
2. Lung Volumes
 Air is forced out of the lungs as the muscles relax. Usually only about 10% of
the air in the lungs is exchanged at each breath (the tidal volume), but up to
70–80% can be exchanged by deep breathing. Tidal volume is the amount of
air that moves in to the lungs with each inspiration (or the amount that moves
out with each expiration). The resting tidal volume in most men and women is
about 500cm3.
 When the deepest possible breath is inspired the excess over the resting tidal
volume is the inspiratory reserve volume: or volume of air that can be taken in
over & above normal inspired tidal volume: about 1.9 liters in women and 3.3
liters in men. At the end of a forced expiration, the air expelled over the tidal
volume is the expiratory reserve volume: in women about 0.7 liters, in men
about 1.0 liter. [The amount of additional air that can be pushed out after the
end of expiratory level of normal breathing].
 The tidal volume and the inspiratory and expiratory reserve volumes represent
the vital capacity of the lungs [or the amount of air that can be forced out of
the lungs after a maximal inspiration). There is a residual volume of air left in
the lungs (about 1.1 liters in women, 1.2 liters in men) which cannot be
expelled (vital capacity + residual volume = total lung capacity …6L in male;
4.7L in female).

5
  The amount of air inspired per minute (pulmonary ventilation, respiratory
minute volume) is normally about 6 L (500 ml/breath x12 breaths/minute).
 The maximal voluntary ventilation (or maximal breathing capacity) is the
largest volume of gas that can be moved in to and out of the lungs in 1 minute
by voluntary effort. Its normal value is 125-170L/min.
 When the alveoli are empty of air, there is a danger that collapse could occur
due to the surface tension of the liquid lining the alveolar surfaces. This is
prevented by the presence of a phospholipid surfactant (a wetting agent)
which reduces this tension. Lack of surfactant in very premature babies causes
major breathing problems: the surfactant appears after about 24 weeks’
gestation.

Respiratory Dead Space

 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.
 Dead space is the portion of each tidal volume that does not take part in gas
exchange.
 There are two different ways to define dead space: (i) anatomic (ii)
physiologic.
 Anatomic dead space is the total volume of the conducting air ways from the
nose or mouth to the level of the terminal bronchioles, and is about 150ml on

6
 average in humans. The anatomic dead space fills with inspired air at the end
of each inspiration but the air is exhaled unchanged.
 Physiological dead space includes all none respiratory parts of the bronchial
tree included in the anatomical dead space, but also factors in alveoli which
are well ventilated but poorly perfused and are therefore less efficient at
exchanging gas with the blood.
 In healthy individuals, the anatomic and physiological dead spaces are roughly
equivalent, since all areas of the lungs are well perfused. However, in disease
states where portions of the lung are poorly perfused, the physiological dead
space may be considerably larger than the anatomical dead space.

CONTROL OF RESPIRATION
 Despite widely differing demands for oxygen uptake and carbon dioxide
output made by the body, the arterial pO2 and pCO2 are normally kept within
close limits. This remarkable regulation of gas exchange is possible because
the level of ventilation is so carefully controlled.
 The three basic elements of the respiratory control system are: 1. Sensors,
which gather information and feed it to the 2. Central Controller in the brain,
which coordinates the information and, in turn, sends impulses to the 3.
Effectors (respiratory muscles), which cause ventilation.

Central Controller
The normal automatic process of breathing originates from impulses which come
from the brainstem.
 The brainstem is the region of the brain that connects the cerebrum with the
spinal cord. It is anterior to the cerebellum.
 It consists of the midbrain, medulla oblongata, and the pons.
Brainstem:
 The periodic nature of inspiration and expiration is controlled by neurons
located in the pons and medulla. These have been designated the respiratory
centers.
 Three main groups of neurons are recognized; medullary respiratory center in
the reticular formation of the medulla, apneustic center in the lower pons, and
the pneumotaxic center in the upper pons.

7
  1. Medullary Respiratory Center in the reticular formation of the medulla: this
comprises two identifiable areas. One group of cells in the dorsal region of the
medulla is associated chiefly with inspiration; the other in the ventral area is
mainly for expiration.
 Cells of the inspiratory area have the property of intrinsic periodic firing and
are responsible for the basic rhythm of ventilation.
 The expiratory area is quiescent during normal quiet breathing because
ventilation is then achieved by active contraction of the inspiratory muscles
(chiefly the diaphragm), followed by passive relaxation of the chest wall to its
equilibrium position. However, in more forceful breathing, e.g. during
exercise, expiration becomes more active as a result of the activity of the
expiratory cells.
 2. Apneustic Center in the lower pons: this area is so named because, if the
brain of an experimental animal is sectioned just above this site, prolonged
inspiratory gasps (apneuses) interrupted by transient expiratory efforts are
seen.
 Apparently, the impulses from this center have an excitatory effect on the
inspiratory area of the medulla.
 3. Pneumotaxic Center in the upper pons: this area appears to ‘switch off’ or
inhibit inspiration and thus regulate respiratory volume and, secondarily,
respiration rate.
 Other Parts of the Brain, such as the limbic system and the hypothalamus, can
affect the pattern of breathing, e.g. in affective states such as rage and fear. As
breathing is under voluntary control to a considerable extent, the cortex can
override the function of the brainstem within limits.
Effectors

8
  The muscles of respiration include the diaphragm, intercostal muscles,
abdominal muscles, and accessory muscles such as the sternomastoids. In the
context of the control of ventilation, it is crucially important that these various
muscle groups work in a coordinated manner, and this is the responsibility of
the central controller.
Sensors
A. Central Chemoreceptors
 A chemoreceptor is a receptor which responds to a change in the chemical
composition of the blood or some other fluid around it. The most important
receptors involved in the minute-by-minute control of ventilation are those
situated near the ventral surface of the medulla in the vicinity of the exit of
the IXth and Xth nerves.
 The central chemoreceptors are surrounded by brain extracellular fluid and
respond to changes in its H+ concentration. An increase in H+ concentration
stimulates ventilation while a decrease inhibits it. The resulting
hyperventilation reduces the pCO2 in the blood.

B. Peripheral Chemoreceptors
 These are located in the carotid bodies at the bifurcation of the common
carotid arteries and in the aortic bodies above and below the aortic arch.
Diagram for Location of Carotid and Aortic Bodies

9
  The peripheral chemoreceptors respond to decreases in the arterial pO2 and
pH and increases in arterial pCO2. The response of these receptors can be
very fast; and their discharge rate can alter during the respiratory cycle as a
result of the small cyclic changes in blood gases.
 The peripheral chemoreceptors are responsible for all the increase of
ventilation that occurs in humans in response to arterial hypoxemia (i.e.
decreased pO2 in arterial blood).
 In humans, the carotid but not the aortic bodies respond to a fall in arterial
pH. Thus, increases in chemoreceptor activity in response to decreases in
arterial pO2 are potentiated by increases in pCO2 and, in the carotid bodies,
decreases in pH.

C. Lung Receptors
(i) Pulmonary Stretch Receptors
 These are believed to lie within airway smooth muscle. They discharge in
response to distension of the lung, and their activity is sustained with lung
inflation. The impulses travel in the vagus nerve via large myelinated fibers.
 The main reflex effect of stimulating these receptors is a slowing of
respiratory frequency due to an increase in expiratory time. This is known as
the Hering-Breuer inflation reflex. Classic experiments showed that inflation
of the lungs tended to inhibit further inspiratory muscle activity. The opposite
is also seen, that is, deflation of the lungs tends to initiate inspiratory activity
(deflation reflex). Thus these reflexes can provide a self-regulatory
mechanism or negative feedback.
 Bilateral vagotomy, which removes the input of these receptors, causes slow,
deep breathing in most animals. However, recent work indicates that the
reflexes are largely inactive in adult humans unless tidal volume is exceeds
one liter, as in exercise.
(ii) Irritant Receptors
 These are thought to lie between airway epithelial cells, and they are
stimulated by noxious gases, cigarette smoke, inhaled dusts, and cold air. The
impulses travel up the vagus in myelinated fibers, and the reflex effects
include broncho-constriction and hyperpnea (increased respiratory rate).

10
  If the stimulus is maintained, the activity of the receptors rapidly lessens, and
they are therefore classified as ‘rapidly adapting’.

(iii) Juxtacapillary (or J) Receptors

 The term juxtacapillary (or J) is used because the receptors are believed to be
in the alveolar walls close to the capillaries. The impulses pass up the vagus
nerve in the slowly conducting non-myelinated fibers and can result in rapid
shallow breathing, although intense stimulation causes apnea (suspension of
external breathing).
 It has been speculated that stimulation of the J receptors may contribute to the
increase in ventilation which occurs on exercise.
 The fourth group of lung receptors has been described; lodged in the airways
but their role is unclear.

11