Lecture Notes on Human Respiratory System Physiology

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LECTURE NOTES ON
HUMAN RESPIRATORY SYSTEM PHYSIOLOGY
(Dr. GÜL ERDEMLI)
CONTENTS
1. MECHANICS OF BREATHING:
2. REGULATION AND CONTROL OF BREATHING:
3. VENTILATION
4. LUNG VOLUMES AND PULMONARY FUNCTION TESTS
5. DIFFUSION
6. PERFUSION
7. GAS TRANSPORT TO THE PERIPHERY
8. ACID-BASE REGULATION
9. RESPIRATORY SYSTEM UNDER STRESS
10. RECOMMENDED FURTHER READING:
11. SELF ASSESSMENT

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1. MECHANICS OF BREATHING :
INSPIRATION: Inspiration is the active part of the breathing process, which is initiated by the
respiratory control centre in medulla oblongata (Brain stem). Activation of medulla causes a
contraction of the diaphragm and intercostal muscles leading to an expansion of thoracic cavity and a
decrease in the pleural space pressure. The diaphragm is a dome-shaped structure that separates the
thoracic and abdominal cavities and is the most important muscle of inspiration. When it contracts, it
moves downward and because it is attached to the lower ribs it also rotates the ribs toward the
horizontal plane, and thereby further expands the chest cavity. In normal quite breathing the diaphragm
moves downward about 1 cm but on forced inspiration/expiration total movement could be up to 10
cm. When it is paralysed it moves to the opposite direction (upwards) with inspiration, paradoxical
movement. The external intercostal muscles connect adjacent ribs. When they contract the ribs are
pulled upward and forward causing further increase in the volume of the thoracic cavity. As a result
fresh air flows along the branching airways into the alveoli until the alveolar pressure equals to the
pressure at the airway opening.
EXPIRATION: Expiration is a passive event due to elastic recoil of the lungs. However, when a great
deal of air has to be removed quickly, as in exercise, or when the airways narrow excessively during
expiration, as in asthma, the internal intercostal muscles and the anterior abdominal muscles contract
and accelerate expiration by raising pleural pressure.
COUPLING OF THE LUNGS AND THE CHEST WALL: The lungs are not directly attached to
the chest wall but they change their volume and shape according to the changes in shape and volume
of the thoracic cavity. Pleura covering the surfaces of the lungs (visceral) or the thoracic cavity
(parietal) together with a thin (20 μm) layer of liquid between them create a liquid coupling.

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PRESSURE-VOLUME RELATIONSHIPS: In the pulmonary physiology absolute pressure means
atmospheric pressure (760 mm Hg at sea levels). The pressures and the pressure differences of the
respiratory system are expressed as relative pressures to the atmospheric pressure. When it is said that
alveolar pressure is zero, it means that alveolar pressure = atmospheric pressure.
If one excises animal lung and places it in a jar, one could measure the changes in volume with a
spirometer through a cannula attached to the trachea. When the pressure inside the jar below
atmospheric pressure, the lung expands and the change in its volume is measured and the pressure-
volume curve is plotted. When there is no pressure distending the lung there is a small volume of gas
in it. As the pressure in the jar is gradually reduced, the volume of the lungs increases. This is initially
a rapid event but after a certain pressure the changes become less evident. It means that the lung is
stiffer when it is expanded and thereby, the pressure-volume curves during inflation and deflation are

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different = hysteresis. Another important point is the volume at a given pressure during deflation is
always larger than during inflation. Even when the pressure outside the lung is increased above the
atmospheric pressure, very little further air is lost and the air is trapped in the alveoli. The volume of
the air trapped in the lung is increased with age and in some respiratory diseases.
COMPLIANCE: The slope of the pressure-volume curve, the volume change per unit pressure is
known as compliance. In normal expanding range (2-10 mm water) the lung is very dispensable, in
other words it is very compliant. The compliance of the human lung is 0.15 L/cm H 2 O. However, it
gets stiffer (compliance smaller) as it is expanded above the normal range. Compliance is reduced
when
(1) The pulmonary venous pressure is increased and the lung becomes engorged with blood
(2) There is alveolar oedema due to insufficiency of alveolar inflation
(3) The lung remains unventilated for a while e.g. atelectasis and
(4) Because of diseases causing fibrosis of the lung e.g. chronic restrictive lung disease.
On the contrary in chronic obstructive pulmonary disease (COPD, e.g. emphysema) the alveolar walls
progressively degenerate, which increases the compliance. The lung compliance is changed according
to the lung size: Obviously the compliance of a mouse lung is much smaller than a human lung. At the
birth the lung compliance is the smallest and increased with age (until adulthood) due to increase in the
size of the lungs. Specific compliance (compliance per unit of lung volume) could be calculated in
order to correct this value for lung size. In asthma (hyperactive airway smooth muscle) the lung
compliance is usually normal.

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The standard procedure for measuring compliance in humans is to determine the pressure-volume
relationship during a passive expiration from total lung capacity. If the lung deflates slowly, alveolar
pressure is equal to atmospheric pressure, and pleural pressure is nearly same as the pressure in the
oesophagus, which is usually measured with a thin-walled balloon attached via a plastic tube to a
pressure-sensor.
CHEST WALL COMPLIANCE: Changes in chest wall compliance are less common than changes
in the lung compliance:
(1) pathologic situations preventing the normal movement of the rib cage, such as,
distortion of the spinal column,
(2) pathologic (cancer) or physiologic (pregnancy) reasons increasing the intra
abdominal pressure,
(3) stiff chest, such as broken ribs.
SURFACE TENSION: A thin film of liquid lines the alveoli and the surface tension of this film is
another important factor in the pressure-volume relationship of the lung. The surface tension arises
because the attractive forces between adjacent molecules of the liquid are much stronger than those of
between the liquid and the gas. As a result of that the liquid surface area becomes as small as possible.
At the interface between the liquid and the alveolar gas, intermolecular forces in the liquid tend to
cause the area of the lining to shrink (the alveoli tend to get smaller). The surface tension contributes
to the pressure-volume behaviour of the lungs because when the lungs are inflated with saline they
have much larger compliance that when they are filled with air (because saline abolishes the surface
tension). This behaviour can clearly be seen in a soap bubble, blown on the end of a tube. The surfaces

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of the bubble contract as much as possible and form the smallest possible surface area, a sphere. This
generates a pressure predicted from Laplace’s law:
Pressure =(4 x surface tension) / radius
The surface tension contributes a large part of the static recoil force of the lung (expiration). The
surface tension changes with the surface area: The larger the area the smaller the surface tension gets.
The most important component of this liquid film is surfactant. It is produced by type 2 alveolar
epithelial cells and its major constituent is dipalmitoyl phosphotidylcholine (DPPC), a phospholipid
with detergent properties. The phospholipid DPPC is synthesised in the lung from fatty acids that are
either extracted from the blood or are themselves synthesised in the lung. Synthesis is fast and there is
a rapid turnover of surfactant. If the blood flow to a region of lung is restricted due to an embolus the
surfactant may be depleted in the effected area. Surfactant synthesis starts relatively late in foetal life
and premature babies without adequate amount of surfactant develop respiratory distress which could
be life threatening.
What are the advantages of having surfactant and the low surface tension?
1. It increases the compliance of the lung
2. It reduces the work of expanding of the lung with each breath
3. It stabilises the alveoli (thus the smaller alveoli do not collapse at the end-expiration)
4. It keeps the alveoli dry (as the surface tension tends to collapse alveoli, it also tends to suck fluid
into the alveolar space from capillaries).
2. REGULATION AND CONTROL OF BREATHING:
In order to maintain normal levels of partial oxygen and carbon dioxide pressure both the depth and
rate of breathing are precisely regulated. Basic elements of the respiratory control system are (1)
strategically placed sensors (2) central controller (3) respiratory muscles.

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CENTRAL CONTROLLER: Breathing is mainly controlled at the level of brainstem. The normal
automatic and periodic nature of breathing is triggered and controlled by the respiratory centres located
in the pons and medulla. These centres are not located in a special nucleus or a group of nuclei but
they are rather poor defined collection of neurones.
1. Medullary respiratory centre:
-Dorsal medullary respiratory neurones are associated with inspiration: It has been proposed that
spontaneous intrinsic periodic firing of these neurones responsible for the basic rhythm of breathing.
As a result, these neurones exhibit a cycle of activity that arises spontaneously every few seconds and
establish the basic rhythm of the respiration. When the neurones are active their action potentials travel
through reticulospinal tract in the spinal cord and phrenic and intercostal nerves and finally stimulate
the respiratory muscles.
-Ventral medullary respiratory neurones are associated with expiration. These neurones are silent
during quite breathing because expiration is a passive event following an active inspiration. However,
they are activated during forced expiration when the rate and the depth of the respiration is increased
e.g. exercise. During heavy breathing increased activity of the inspiratory centre neurones activates the
expiratory system. In turn, the increased activity of the expiratory system inhibits the inspiratory centre
and stimulates muscles of expiration. The dorsal and ventral groups are bilaterally paired and there is

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cross communication between them. As a consequence they behave in synchrony and the respiratory
movements are symmetric.
2.Apneustic Centre: It is located in the lower pons. Exact role of this centre in the normal breathing is
not known. Lesions covering this area in the pons cause a pathologic respiratory rhythm with increased
apnoea frequency. What is known is nerve impulses from the apneustic centre stimulate the inspiratory
centre and without constant influence of this centre respiration becomes shallow and irregular.
3.Pneumotaxic centre: It is located in the upper pons. This centre is a group of neurones that have an
inhibitory effect on the both inspiratory and apneustic centres. It is probably responsible for the
termination of inspiration by inhibiting the activity of the dorsal medullar neurones. It primarily
regulates the volume and secondarily the rate of the respiration. Because in the lesions of this area
normal respiration is protected it is generally believed that upper pons is responsible for the fine-tuning
of the respiratory rhythm. Hypoactivation of this centre causes prolonged deep inspirations and brief,
limited expirations by allowing the inspiration centre remain active longer than normal.
Hyperactivation of this centre on the other hand results in shallow inspirations. The apneustic and
pneumotaxic centres function in co-ordination in order to provide a rhythmic respiratory cycle:
Activation of the inspiratory centre stimulates the muscles of inspiration and also the pneumotaxic
centre. Then the pneumotaxic centre inhibits both the apneustic and the inspiratory centres resulting in
initiation of expiration. Spontaneous activity of the neurones in the inspiratory centre starts another
similar cycle again.
Breathing in some extent is also controlled consciously from higher brain centres (e.g. cerebral cortex).
This control is required when we talk, cough and vomit. It is also possible voluntarily change the rate
of the breathing. Hyperventilation can decrease blood partial carbon dioxide pressure (PCO2 ) due to
loss of CO2 resulting in peripheral vasodilatation and decrease in blood pressure. One can also stop
breathing voluntarily. That results in an increase in arterial partial oxygen pressure (PO2 ), which
produces an urge to breathe. When eventually PCO2 reaches the high enough level it overrides the
conscious influences from the cortex and stimulates the inspiratory system. If one holds his breath long
enough to decrease PO2 to a very low level one may loose his consciousness. In an unconscious person
automatic control of the respiration takes over and the normal breathing resumes.
Other parts of the brain (limbic system, hypothalamus) can also alter the breathing pattern e.g.
affective states, strong emotions such as rage and fear. In addition, stimulation of touch, thermal and
pain receptors can also stimulate the respiratory system.