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1

LECTURE NOTES ON
HUMAN RESPIRATORY SYSTEM PHYSIOLOGY
(Dr
...
MECHANICS OF BREATHING:
2
...
VENTILATION
4
...
DIFFUSION
6
...
GAS TRANSPORT TO THE PERIPHERY
8
...
RESPIRATORY SYSTEM UNDER STRESS
10
...
SELF ASSESSMENT

2

1
...
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
...
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
...
When it is paralysed it moves to the opposite direction (upwards) with inspiration, paradoxical
movement
...
When they contract the ribs are
pulled upward and forward causing further increase in the volume of the thoracic cavity
...


EXPIRATION: Expiration is a passive event due to elastic recoil of the lungs
...

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
...


3

PRESSURE-VOLUME RELATIONSHIPS: In the pulmonary physiology absolute pressure means
atmospheric pressure (760 mm Hg at sea levels)
...
When it is said that
alveolar pressure is zero, it means that alveolar pressure = atmospheric pressure
...
When the pressure inside the jar below
atmospheric pressure, the lung expands and the change in its volume is measured and the pressurevolume curve is plotted
...
As the pressure in the jar is gradually reduced, the volume of the lungs increases
...
It means that the lung is
stiffer when it is expanded and thereby, the pressure-volume curves during inflation and deflation are

4

different = hysteresis
...
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
...


COMPLIANCE: The slope of the pressure-volume curve, the volume change per unit pressure is
known as compliance
...
The compliance of the human lung is 0
...
However, it
gets stiffer (compliance smaller) as it is expanded above the normal range
...
g
...
g
...

On the contrary in chronic obstructive pulmonary disease (COPD, e
...
emphysema) the alveolar walls
progressively degenerate, which increases the compliance
...
At the
birth the lung compliance is the smallest and increased with age (until adulthood) due to increase in the
size of the lungs
...
In asthma (hyperactive airway smooth muscle) the lung
compliance is usually normal
...
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
...


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
...
As a result of that the liquid surface area becomes as small as possible
...
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)
...
The surfaces

6

of the bubble contract as much as possible and form the smallest possible surface area, a sphere
...
The
surface tension changes with the surface area: The larger the area the smaller the surface tension gets
...
It is produced by type 2 alveolar
epithelial cells and its major constituent is dipalmitoyl phosphotidylcholine (DPPC), a phospholipid
with detergent properties
...
Synthesis is fast and there is
a rapid turnover of surfactant
...
Surfactant synthesis starts relatively late in foetal life
and premature babies without adequate amount of surfactant develop respiratory distress which could
be life threatening
...
It increases the compliance of the lung
2
...
It stabilises the alveoli (thus the smaller alveoli do not collapse at the end-expiration)
4
...


2
...
Basic elements of the respiratory control system are (1)
strategically placed sensors (2) central controller (3) respiratory muscles
...
The normal
automatic and periodic nature of breathing is triggered and controlled by the respiratory centres located
in the pons and medulla
...

1
...

As a result, these neurones exhibit a cycle of activity that arises spontaneously every few seconds and
establish the basic rhythm of the respiration
...

-Ventral medullary respiratory neurones are associated with expiration
...
However,
they are activated during forced expiration when the rate and the depth of the respiration is increased
e
...
exercise
...
In turn, the increased activity of the expiratory system inhibits the inspiratory centre
and stimulates muscles of expiration
...
As a consequence they behave in synchrony and the respiratory
movements are symmetric
...
Apneustic Centre: It is located in the lower pons
...
Lesions covering this area in the pons cause a pathologic respiratory rhythm with increased
apnoea frequency
...

3
...
This centre is a group of neurones that have an
inhibitory effect on the both inspiratory and apneustic centres
...
It primarily
regulates the volume and secondarily the rate of the respiration
...
Hypoactivation of this centre causes prolonged deep inspirations and brief,
limited expirations by allowing the inspiration centre remain active longer than normal
...
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
...
Spontaneous activity of the neurones in the inspiratory centre starts another
similar cycle again
...
g
...

This control is required when we talk, cough and vomit
...
Hyperventilation can decrease blood partial carbon dioxide pressure (PCO2) due to
loss of CO2 resulting in peripheral vasodilatation and decrease in blood pressure
...
That results in an increase in arterial partial oxygen pressure (PO2), which
produces an urge to breathe
...
If one holds his breath long
enough to decrease PO2 to a very low level one may loose his consciousness
...

Other parts of the brain (limbic system, hypothalamus) can also alter the breathing pattern e
...

affective states, strong emotions such as rage and fear
...


9

RESPIRATORY MUSCLES: Diaphragm, intercostal muscles and the other accessory respiratory
muscles work in co-ordination for normal breathing under central controller
...


10

SENSORS:
1
...
Inflation
of the lungs activates these receptors and activation of the stretch receptors in turn inhibits the
neurones in inspiratory centre via vagus nerve
...
This
phenomenon is called Hering-Breuer Reflex
...
In adults it is
functional only during exercise when the tidal volume is larger than normal
...
CHEMORECEPTORS: The respiratory system maintains concentrations of O2, CO2 and the pH of
the body fluids within the normal range of values
...
Chemoreceptors are specialised neurones activated by changes in O2 or
CO2 levels in the blood and the brain tissue, respectively
...
O2-sensitive chemoreceptors (Peripheral
chemoreceptors) are located at the bifurcation of the carotid artery in the neck and the aortic arch
...
They are connected to
the respiratory centre in the medulla by glossopharingeal nerve (carotid body chemoreceptors) and the
vagus nerve (aortic body)
...
They actually respond to changes in H+ concentration in these compartments
...

(When CO2 combines with water forms carbonic acid and liberates H+ and HCO3-)
...
Cerebral vasodilatation always accompanies an increased PCO2
and enhances the diffusion of CO2 into the CSF
...
As a result changes in pH for a given change in PCO2 is always bigger
than the change in blood
...
It is much more important than oxygen to maintain
normal respiration
...
Hypocapnia, lower than normal PCO2 level in the blood causes in periods in which
respiratory movements do not occur
...
A decrease in PO2 is called hypoxia and only after 50 % decrease in PO2 can
produce significant changes in respiration
...
Consequently only big changes in PO2 produce
symptoms otherwise it is compensated by O2, which is bound with Hb
...
At high altitude because the ability of the
lung to eliminate CO2 is not affected, in response to increased respiration, blood PCO2 is decreased
...


3
...
The conducting airways consist of a series of branching
tubes which become narrower, shorter and more numerous as they penetrate deeper into the lung
...
This process continues down to the terminal bronchioles, which are the smallest airways
without alveoli
...
Its volume is about 150 ml but it varies because airways are not
rigid; during inspiration, respiratory tubes are lengthened and dilated, especially in deep breathing
...
The very first barrier starts at the vestibules of the
nose, which contain hairs, and healthy, sticky mucus intercepting air-borne particles
...
Various factors
can interfere with ciliary activity: for example nicotine and tar in tobacco smoking
...
The
larynx and the bifurcation of the trachea are the most sensitive regions and any particles of foreign
matter lodged in these regions are removed when a cough sends a rapid blast of air sweeping out the
respiratory tree
...

This zone is called respiratory zone and the gas exchange occurs here
...
5 to 3 L
...
The capillaries lie in the walls of the alveoli and form a dense network that the blood
continuously runs in the alveolar wall
...
g
...
The diameter of a capillary segment is
about 10 µm, just large enough for a red blood cell
...
This enables the high blood flow to the
circuit
...
LUNG VOLUMES AND PULMONARY FUNCTION TESTS:

Pulmonary function can be examined by the spirometry technique
...
The subject breathes into a closed system in which air is trapped
(bell)
...
Corresponding movements of an attached pen register the change in
volume on a rotating drum recorder
...
5 L)
...
2 L)
...
6 L)
(TV+IRV)
Functional Residual Capacity (FRC): The volume of gas that remains in the lung at the end of a
passive expiration
...
5 L or 40 % of the maximal lung volume) (ERV+RV)
...

(1-1
...


Total Lung Capacity (TLC): The maximal lung volume that can be achieved voluntarily
...
(4-5 L) (IRV+ERV+TV)
...
During exercise the tidal volume and the number of breaths per minute increase to
produce a total minute volume as high as 100 to 200 L/min
...
After some breathes the amount of helium in the lung and the
spirometer reach equilibrium
...


15

V1 = C2 x (V1 + V2)
V2 = V1 x (C1 – C2) / C2
V2 = FRC
Another way of measuring FRC is with a body plethysmograph
...
At the end of a normal expiration, the mouthpiece is shut and the subject makes
respiratory efforts
...

The Boyle’s law can also be applied to the gas in the lung:

P3 x V2 = P4 x (V2 + ∆V)
V2 = FRC
P3,4: Mouth pressures before (P3) and after (P4) the respiratory efforts
...
Normally measurements with these techniques are similar
...

TOTAL VENTILATION: The total volume of the gas leaving the lung per unit time
...
It can be measured by having the subject breath through a
valve that separates the inspired air from expired air and collecting the expired air
...

However, not all of the total ventilation volume reaches the alveoli
...
Thus, the volume of gas entering the respiratory zone, alveolar ventilation, is
(500-150) x 15 = 5250 ml/min
...
One way is
to measure the volume of anatomic dead space and calculate the dead space ventilation
...

Alveolar ventilation = Total ventilation – Anatomic death space ventilation
Anatomic dead space ventilation = Anatomic dead space volume x respiration frequency
VE: total expiration volume
VT: Tidal volume
VD: Dead Space volume
VA: volume of alveolar gas during tidal breathing
V: volume per unit time

VT = VD + VA

17

(VT x n) = (VD x n) + (VA x n)
V: volume per unit time
VE: Expired total ventilation
VD: dead space ventilation
VA: alveolar ventilation

VE = VD + VA
VA = VE - VD
The disadvantage of this method is it is not very easy to determine dead space volume without a
considerable error
...
Since
the amount of CO2 in the inspired air is negligible and no gas exchange occurs, we could assume that
there is CO2 in the anatomic dead space
...


VCO2 = VA x % CO2 / 100
VCO2 = the volume of CO2 exhaled per unit time
...
It is approximately 150 ml but
its volume increases with large inspiration and depends on the size and the posture of the subject
...
After
a single inspiration of pure oxygen (100 %) nitrogen concentration in the expired air is increased as the
gas in the dead space is washed by pure oxygen
...
The dead space is found by plotting nitrogen concentration against the expired
volume
...


18

PULMONARY FUNCTION TESTS : Pulmonary function tests are very useful tests to diagnose
several lung diseases
...

TESTS OF VENTILATORY CAPACITY
Forced Expiratory Volume (FEV): It is the volume of gas exhaled in one second by a forced
expiration following a full inspiration (FEV1)
...
However, this value could be slightly smaller than the vital
capacity measured with a slow (normal speed) expiration
...
The normal ratio of the FEV1 is 80 % of FVC
...
It is obtained by identifying the 25 % and 75 % volume
points of FVC, measuring the time between these points and calculating the flow rate
...
In restrictive lung diseases
(such as pulmonary fibrosis), the vital capacity is reduced to below normal levels
...
In obstructive lung disease (such as asthma,
emphysema, bronchitis) the vital capacity is normal because lung tissue is not damage and its
compliance is unchanged
...
Although the vital capacity is normal, the increased airway
resistance makes expiration more difficult and takes longer time
...
A
significant decrease in these values suggests an obstructive lung disease
...
DIFFUSION
...
It is a passive
process which means requires no energy
...

Because the blood-gas barrier in the lung is extremely thin and has a very large area (50-100 m2), it is
well suited to its function
...
There are about 300 million alveoli in the human
lung, creating 85 m2 surface area but having a volume of only 4 L
...


Pdry atmosphere = PN2 + PO2 + PCO2 = 760 mmHg
Since oxygen constitutes 21 % of the atmosphere, PO2 = 159 mm Hg
...
However when the
inspired air arrived the alveoli it is normally saturated with water vapour
...
21 (760-47) = 150 mm Hg (oxygen partial pressure of the inspired air when it arrives alveoli,
before the gas exchange)
...
The actual amount of
dissolved O2 is a linear function of the PO2: The higher PO2 indicates that more O2 is dissolved
...
A
normal PO2 in the inspired air together with low arterial PO2 means that the gas exchange in the lungs

21

is impaired
...


Inspired Air

Alveolar Air

H2 O

Variable

47 mm Hg

CO2

0
...
However, CO forms very tight bonds with Hb that even though large amount of CO
is taken up by the red blood cells almost no increase in the CO partial pressure is observed
...


The other extreme example is nitrous oxide: Nitrous oxide diffuses across the barrier but forms no
combination with Hb
...
The amount of nitrous oxide
taken up by blood depends on the amount of blood available: perfusion limited
...
It does bind to Hb but nothing like the avidity of CO
...


22

Thus, in normal, physiological condition oxygen transfer is perfusion limited
...
g
...
PO2 of
the venous blood and the alveolar air is 40 and 100 mm Hg, respectively
...
During exercise the pulmonary blood flow
is increased and the average travel time of a red blood cell in the capillary is shortened
...
On the other hand if there is thickening of alveolar wall oxygen transport would
be impaired and measurable difference between alveolar gas and end-capillary blood PO2 occurs
...
D
...


VGas = DL
...


DL = VCO / (P1 – P2)
Since CO in the capillary blood is negligible

DL = VCO / (PACO)
The diffusing capacity of the lung for CO is the volume of CO transferred in mm per mm Hg of
alveolar partial pressure
...

Steady state method: A subject breathes low concentration of CO until steady state is reached
...
The normal value is 25
ml/min/mm Hg
...
Solubility of CO2 is higher and it
diffuses through tissue 20 times faster than oxygen
...


5
...
It begins at the main pulmonary artery, which receives the mixed venous
blood pumped by the right ventricle
...

Each time the airway branches, the arterial tree branches that the two parallel each other
...
In addition, pulmonary vessels protect the body from obstruction of important vessels in other
organs such as renal or cerebral vessels
...
g
...
The pulmonary circulation serves as a blood reservoir and the
volume in the lung capillaries is approximately equal to the stroke volume of the right heart
...
For example angiotensin
I is activated and converted to angiotensin II by angiotensin-converting enzyme which is located on
the surface of the endothelial cells of the pulmonary capillaries
...
The pressures in the pulmonary circulation are remarkably low: The pressure in the main pulmonary
artery is 25 mm Hg (systolic) and 8 mm Hg (diastolic), in average 15 mm Hg
...

2
...
This anatomical
adaptation of the lung is critically important for its function: The lung is required to receive the

24

whole of the cardiac output at all times
...

3
...

4
...
Two mechanisms are responsible for this function
...
Capillary recruitment: opening of initially closed capillaries when cardiac output increases
...
Capillary distension: The decrease in pulmonary pressure with increased cardiac output has
several beneficial effects: It (1) minimise the load on the right heart, (2) prevents pulmonary
oedema, (3) maintains the adequate flow rate of the blood in the capillary and (4) increases the
capillary surface area
...
GAS TRANSPORT TO THE PERIPHERY

(How do gases move to the

peripheral tissues?)
OXYGEN:
Oxygen is carried in the blood in two forms, dissolved and combined with haemoglobin (Hb)
...
100 ml of arterial blood with normal oxygen partial pressure (100 mm Hg) contains
0
...
By this way amount of oxygen delivered to the tissues is only about 90 ml/min
...


HAEMOGLOBIN:
Haemoglobin (Hb) = Heme (iron-porphyrin) + globin (protein)
Globin has 4 protein polypeptide chains: 2 alpha (each has 141 aa) and 2 beta (each has 146 aa)
...

Hb-A: Normal adult Hb
Hb-F: Foetal Hb, which makes part of the total Hb at birth and is gradually, replaced by Hb-A
...
This Hb has valine in the beta chain instead of glutamic acid
...
The fragility of the red
cells is increased and there is a tendency to thrombus formation
...
In the centre of each heme group there is one atom of iron, which can combine
with one oxygen molecule
...
Heme contains iron
in the reduced form (Fe++, ferrous iron)
...
Oxygen forms a reversible combination with Hb
...
Oxyhemoglobin is not same with oxidised
Hb (or methemoglobin) in which iron is in the oxidised (Fe+++, ferric) form
...

The oxygen carrying capacity of the blood is determined by the Hb concentration
...
When the Hb concentration is
high, polycythemia, the oxygen carrying capacity of the blood is increased
...
Its production is stimulated when the amount of oxygen delivered to the kidneys is
lower than normal
...


The oxygen saturation of Hb

O2 combined with Hb / O2 capacity
One gram of Hb can combine with 1
...
8 ml
...
5 % while oxygen saturation of the
venous blood (PO2= 40 mm Hg) is 75 %
...
In such patient with normal respiratory
functions (PO2=100 mm Hg), O2 capacity will be lower (20
...
9 ml/100 ml blood) and
though the O2 saturation still be 97
...

Because the reduced Hb is purple a low arterial oxygen saturation causes cyanosis
...
A rightward shift means more unloading of oxygen at
a given PO2 in a tissue capillary
...
g
...

Because CO has a much higher affinity to Hb (forms carboxyhemoglobin, COHb), even small amounts
of CO bind the large proportion of Hb making it unavailable for oxygen: The Hb concentration and
PO2 of blood may be normal but its oxygen content is grossly reduced
...

Dissolved CO2: Because CO2 is more soluble than oxygen this fraction of CO2 in the blood plays an
important role in its transport (about 10%)
...
When the concentrations of the products of the
carbonic acid dissociation reaction bicarbonate diffuses into the blood but not hydrogen ion because
the red cell membrane is relatively impermeable to the positively charged ions
...
Some of the H+ are bound to Hb:

H+ + HbO2 £ H+Hb + O2
The reduced Hb is a better proton acceptor than oxygenated Hb meaning deoxygenation of the blood
increases its ability to carry CO2 = Haldane effect
...
Such as
(the most important one) globin of Hb (carbamino-haemoglobin)
...
In venous blood these values are 60, 30 and 10, respectively
...
ACID-BASE REGULATION
By altering the CO2 elimination the lungs can control the acid-base balance of the body
...
03 PCO2)
pH = 6
...
03x40
pH = 6
...
1 + 1
...
4
In the human body bicarbonate concentration is regulated by mainly the kidneys and the PCO2 by the
lungs
...
g
...
Whenever PCO2 is increased the bicarbonate concentration is also rises due to

30

dissociation of carbonic acid but nevertheless HCO3-/PCO2 falls
...


pH = 6
...
03 x 40 = 6
...
4

(Normal)

pH = 6
...
03 x 60 = 6
...
6 = 7
...
1 + log 33 / 0
...
1 + log18
...
36 (compensated res
...
g
...
The kidneys compensate it by
increasing the HCO3- excretion
...
In this case HCO3-/PCO2 decreases
by lowering HCO3- in the blood
...
g
...

This stimulation is mainly due to stimulation of peripheral chemoreceptors by H+
...
Common reasons are
excessive ingestion of alkalis and loss of gastric acid due to vomiting
...


9
...
This increase in
ventilation (hyperpnea) matches the simultaneous increase in oxygen consumption and carbon
dioxide production that the arterial blood carbon dioxide and oxygen partial pressures and pH do not
change dramatically (Please note that hyperpnea is different from hyperventilation
...
The mechanism underlying the exercise-induced changes in ventilation is not
clear
...
Neurogenic mechanisms: (1) stimulation of respiratory system muscles by sensory nerve activity
from exercising limbs, probably via activating brain stem respiratory centres and/or via spinal reflexes
...

2
...
However, the focal changes in these
parameters near chemoreceptor area may contribute to the exercise-induced changes in ventilation
...
Lactic acid concentration is increased due to
anaerobic limitations in the muscle cells during heavy exercise
...
Oxidative phosphorylation is an oxygen consuming process by which energy derived from substrate
oxidation is stored in ATP as a chemical energy
...
g
...
g
...
]

ACCLIMATIZATION TO HIGH ALTITUDE: In the high altitude the human body compensates
the low partial oxygen pressure by changing ventilation or affinity of Hb to oxygen or total Hb
concentration
...

This lowers the arterial partial carbon dioxide pressure and causes respiratory alkalosis
...
Hyperventilation
increases the tidal volume and reduces the proportion of the anatomical death space in the inspired air
...
However, in spite of all these adaptation
mechanisms, the partial oxygen pressure in the arterial blood can not be increased more than the partial
oxygen pressure in the inspired air
...
At sea levels arterial blood loses 22% of its oxygen load in tissues:
The oxygen saturation of the arterial and venous blood is 97% and 75%, respectively
...
However, at very high
altitudes increase in blood pH causes a shift to the left in the oxygen saturation curve and increases the
affinity of Hb to oxygen
...
Due to low oxygen partial pressure in the arterial blood at high
altitude the tissue hypoxia occurs and in response the kidneys secrete erythropoietin hormone
...


32

10
...
Anatomy & Physiology by Rod R
...
Stephens and Philip Tate McGraw Hill,
International edition
...
Respiratory Physiology, the essentials by John B West, Williams and Wilkins, (USA)
...
Pulmonary Pathophysiology, the essentials by John B West, Williams and Wilkins, (USA)
...
Principles of Anatomy and Physiology by G
...
Tortora and S
...
Grabowski, Harper Collins College
Publishers (USA)
...
Principles of Physiology by R
...
Berne and M
...
Levy, Mosby (USA)
...
Medical Physiology by R
...
Rhoades & G
...

7
...
M
...
R
...
C
...


33

11
...
How is a respiratory bronchiole distinguished from a terminal bronchiole?
2
...
Which of the following lung volumes cannot be measured with a simple spirometer?
(1) vital capacity,
(2) functional residual capacity,
(3) tidal volume,
(4) residual volume
4
...
What is pulmonary sulfactant and what happens in case of its insufficiency?
6
...
What is the Hering-Breuer reflex and its role in normal breathing in adults?
8
...
What is the role of respiratory centres located in the pons in the control of breathing?
10
...
What are the main changes occur at high altitudes?
12
...
Patients with ventilation-perfusion inequality have hypoxemia but no CO2 retention
...
What is chloride shift?
15
...
What is the difference between that hyperpnea and hyperventilation?
17

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