Transcript 46f818a33437a16

Learning objectives
Pulmonary structure and mechanics.
Gas transport and exchange.
Regulation of respiration.
Why We Breathe?
We need to breathe because our cells
require oxygen for cellular respiration and
must remove carbon dioxide from the cell as
a by-product of the cellular respiration
(metabolism).
What is the respiratory system?
Your respiratory system is made up
of the organs in your body that help
you to breathe. Remember, that
Respiration = Breathing.
Respiration
Respiration means taking up of oxygen (O2), its
utilization in the tissues and removal of carbon
dioxide (CO2).
In the process, O2 is drawn in as a part of
inspired air and then taken up by blood from
the lungs.
O2 is then transported by blood to the tissues
where it is used up and CO2 is produced.
This CO2 is again taken up by blood and
delivered to the lungs wherefrom the CO2 is
expelled through the expired air.
O2 & CO2 exchange between body tissues & environment
Atmospheric
air contains
approx. 21%
O2; 79% N2
and 0.04%
CO2.
Types of Respiration
The general term respiration refers to two integrated
processes: external respiration and internal respiration.
External respiration
It is the process of bringing air from the external
environment and transporting it to the cell while CO2 is
carried from the cell to the external environment.
The process of external respiration involves three
major events: pulmonary ventilation, pulmonary
diffusion and transport of gases.
Internal respiration (cellular respiration)
It consists of a series of complex metabolic reactions
that utilizes O2 and releases CO2 and energy.
Overview of
External &
Internal
Respiration
Functional anatomy of the respiratory system
The respiratory system consists of the upper
respiratory tract includes the mouth, nose, pharynx
and larynx;
The lower respiratory tract starts at the trachea,
and includes bronchi and lungs.
The two lungs are enclosed within the thoracic cage
which is formed by the ribs, sternum, vertebral
column and the dome-shaped diaphragm.
The diaphragm is separating the thorax from the
abdomen.
The left lung has two lobes and the right has three.
Each lung lobe is made up of several
bronchopulmonary segments.
Pleura
The lungs are covered by a thin membrane
(visceral pleura) and inside surface of the
thoracic cage is lined by another thin
membrane, parietal pleura.
The tiny space between the two pleura is called
pleural cavity which is filled with the ultrafiltrate
of plasma called pleural fluid (about 10ml)
helps in lubrication of the pleura.
Tracheobronchial Tree
The airway tree consists of a series of highly branched
hollow tubes that decrease in diameter and become
more numerous at each branching (refers by their
generation number).
Trachea (zero generation), the main airway in turn
branches into two bronchi (first generation), one of
which enters each lung.
There is a total of approximately 23 generations of
airways.
Tracheobronchial Tree
(23 generations of airways)
As generation number increases (airways become
smaller), the amount of cilia, the number of mucussecreting cells, the presence of submucosal glands
and the amount of cartilage in the airway walls all
gradually decrease.
Airways maintain some cartilage to about 10th
generation, up to which point they are referred to as
bronchi. At about the 11th and succeeding
generations, the now cartilage-free airways are called
bronchioles.
The cartilage is important for preventing airway
collapse. The mucus is important for trapping small
foreign particles. The cilia sweep the carpet of mucus
and kept moist by secretions.
Bronchial tree: Trachea→ bronchi→ smaller
bronchi→ terminal bronchioles.
Wall of Tracheobronchial Tree
Respiratory air passages
Functionally, the respiratory air passages are
divided into two zones:
– Conductive zone and
– Respiratory zone
Conducting zone
The first 16 subdivisions (from trachea to
terminal bronchioles) form conducting zone of
airway.
The terminal bronchioles redivide to form
respiratory bronchioles and then to alveolar
ducts and sacs which end as alveoli.
The conducting zone of the respiratory system, in
summary consists of the following parts:
Mouth→ nose→ pharynx→ larynx→ trachea→
bronchi→ all successive branches of bronchioles
including terminal bronchioles.
No gas exchange occurs in these regions. The
amount of air present in these regions is called
‘’anatomical dead space’’.
The quantity of air present in these regions is about
150 ml.
The remaining subdivisions form the transitional
and respiratory zone where gas exchange occurs.
Functions of conducting zone
1. Warming and cooling of inspired air
2. Moistening or humidification of the inspired air
3. Filtration and cleaning
4. Secretion of IgA in the bronchial secretions, an
additional protection against respiratory infections
5. Tonsils and adenoids, immunologically active
lymphoid tissue in the pharynx
6. Distribute air to the gas exchange surface of the lung.
Respiratory zone
The respiratory zone includes the respiratory
bronchiole which opens into a number of
alveolar ducts and each alveolar duct opens
into number of alveoli. Alveoli are tiny air sacs,
having a diameter of 0.25 mm. There are about
300 million alveoli in the two lungs.
Acinus
The acinus is the functional or terminal respiratory unit
of the lung and includes all structures from respiratory
bronchiole to the alveolus (alveolar ducts, alveolar
sacs and alveoli).
An acinus averages 0.75 mm diameter.
Each person has about 20,000 acini.
Acinus
The alveolar surface
The alveolar lining consists of two distinct types of
epithelial cells, type-I and type-II alveolar
pneumocytes.
The elongated type I cells cover 90% to 95% of the
alveolar surface, and it is the primary site for gas
exchange.
The cuboidal type-II cells are secreting surfactant,
responsible for preventing the collapse of lungs.
After an injury, type-I cells degenerate, whereas typeII cells proliferate and line the alveolar space
(repairing cell).
Third types of cells, the pulmonary alveolar
macrophage, are found which ingest the inhaled
bacteria and small particles.
Muscular wall of respiratory passageways and its
control:
The rings of cartilage in the walls of the trachea and
bronchi prevent them from collapse.
The smooth muscle fibers in their walls can alter
(change) the size of their lumen and vary airway
resistance.
The terminal bronchioles have abundant of smooth
muscle and no cartilage but the respiratory
bronchioles are occupied by pulmonary epithelium
and underlying fibrous tissue plus few smooth muscle
fiber.
These respiratory smooth muscles are richly
innervated by cholinergic parasympathetic nerve
fibers.
Their stimulation causes mild to moderate bronchial
constriction.
Histamine and slow reactive substance of anaphylaxis
are potent broncho-constrictor. During allergic
reactions, these are released by mast cells in the lung
tissues.
Direct control of the bronchioles by sympathetic nerve
fiber is relatively weak but bronchial smooth fibers
contain β2 adrenergic receptors.
Therefore, they respond to circulating epinephrine and
norepinephrine (from adrenal medulla) and inhaled or
injected
sympathomimetic
drugs
(salbutamol,
isoproterenol etc,) resulting in bronchodilation.
learning objectives
Pulmonary circulation& pressure
Ventilation
Circulation through lungs
The lungs receive blood from two sources:
1. The bronchial circulation and
2. The pulmonary circulation.
Bronchial circulation
It accounts for only a small part of the cardiac
output (~2%). The walls of the large airways
are supplied by bronchial circulation
(oxygenated blood) through bronchial arteries
from the aorta.
Pulmonary circulation
The output of the right ventricle passes through the
pulmonary artery, branched and supplies the
individual alveoli of the lung.
The capillaries lie in the walls of the alveoli. This
network is so dense that the blood forms almost a
continuous sheet in the alveolar wall.
There may be about 1000 pulmonary capillaries per
alveolus.
The entire pulmonary vasculature is a distensible lowpressure system (normal pulmonary capillary pressure
is 7 mm Hg).
Capillary fluid exchange in the lung and
pulmonary interstitial fluid dynamics
1.
2.
3.
4.
The differences in fluid dynamics between lung
capillary membranes and peripheral tissues:
The pulmonary capillary pressure is low about 7 mm
Hg (peripheral tissue pressure 17 mm Hg).
The interstitial fluid pressure in the lung is slightly
negative than peripheral tissue.
Pulmonary capillaries are leaky to protein molecules,
so oncotic pressure is 14 mmHg (28 mmHg in
peripheral tissues).
Alveolar walls are extremely thin and the alveolar
epithelium covering the alveolar surfaces is so weak
that it can be ruptured by any positive pressure in the
interstitial spaces greater than alveolar air pressure
(greater than 0 mm Hg).
Interrelations between interstitial fluid pressure
and other pressures in the lung
Forces tending to cause movement of fluid outward from the
capillaries and into the pulmonary interstitium:
mmHg
Capillary pressure
7
Interstitial fluid colloid osmotic pressure (oncotic pressure) 14
Negative interstitial fluid pressure (ISF)
8
Total outward force
29
Forces tending to cause absorption of fluid to the capillaries:
Plasma Colloid osmotic pressure
28
Total inward force
28
Therefore, the mean filtration pressure is (29-28) = +1 mm
Hg.
Negative pulmonary interstitial pressure and the mechanism
for keeping alveoli dry
This filtration pressure causes a slight continual flow of
fluid from the pulmonary capillaries into the interstitial
space.
Small amount evaporates in the alveoli.
Rest of the fluid is pumped back to the circulation
through the pulmonary lymphatic system.
Negative interstitial fluid pressure and the
mechanism for keeping alveoli dry
There are small pores between alveolar epithelial cells
(pores of Kohn) through which water, electrolytes
and even protein molecules can pass.
However, alveoli do not fill with fluid (kept dry)
because the negative ISF helps the absorption of fluid.
Whenever, fluid appears in the alveoli, it will be simply
sucked mechanically into the lung interstitium through
the small pores. The excess fluid in lung ISF is carried
away through pulmonary lymphatics.
Thus, under normal condition, the alveoli are kept in a
‘dry state’ except for a small amount of fluid that
seeps from the alveoli to keep them moist.
Pulmonary edema
An organ which is very much sensitive to proper fluid
balance is the lung.
Slight increases in the hydrostatic pressure of the
pulmonary capillaries can lead to pulmonary edema.
This condition decreases the pulmonary compliance
(making lung expansion more difficult).
It may severely compromises gas exchange across
the pulmonary capillary bed.
Acute pulmonary edema is a life-threatening condition.
Causes of pulmonary edema
(a) Left heart failure
Pulmonary edema is often associated with left heart
failure.
Contractile properties of the left ventricle are
inadequate to eject all of the blood that enters from the
lungs.
This causes a sharp rise in left end- diastolic volume
and pressure and a resultant increase in pulmonary
venous and capillary pressures causing pulmonary
edema.
(b) Damage to the pulmonary blood capillary
membranes
Damage to the pulmonary blood capillary membranes
caused by infection such as pneumonia.
Breathing noxious substances (chlorine gas, sulfur
dioxide gas) cause rapid leakage of plasma proteins
and fluid out of the capillaries into both the lung
interstitial spaces and the alveoli.
(c) Rapid infusion of intravenous fluids or blood
transfusion
Hypervolemia due to rapid infusion of intravenous
fluids or blood transfusion may cause pulmonary
edema.
Functions of the Respiratory System
Primary Function
Exchange of oxygen and carbon dioxide
Secondary Functions
Voice production
Regulation of plasma pH (acid-base balance)
Temperature regulation
Sense of smell
Infection prevention (lysozyme, IgA, PAM)
Metabolic function (synthesis of surfactant, conversion of
angiotensin I to II, formation of bradykinin, histamine, serotonin,
heparin, prostaglandins).
Events of Respiration
The goals of respiration are to provide O2 to the
tissues and to remove CO2.
To achieve these goals, respiration can be divided
into four major functional events:
Pulmonary ventilation: the inflow and outflow of air
between the atmosphere and the lung alveoli.
. Diffusion of O2 and CO2 between the alveoli and the
blood.
. Transport of O2 and CO2 in the blood to and from the
cells.
. Regulation of respiration.
.
Pulmonary ventilation
Movement of air from the conducting zone to the
terminal bronchioles occurs as a result of the pressure
differences between the two ends of the airways.
Airflow through the bronchioles is directly proportional
to the pressure difference and inversely proportional to
the frictional resistance to flow (airway resistance).
The pressure differences in the pulmonary system are
induced by:
– Lung volumes
– Compliance and elasticity
– Surface tension
The Muscles of Respiration
Primary Muscles
The Diaphragm
External and Internal Intercostal Muscles
Accessory Muscles
Sternocleidomastoid
Scalene
Muscles of shoulder girdle
Abdominal Muscles
Muscles of Inspiration
Primary Muscles
The Diaphragm
External Intercostal Muscles
Accessory Muscles
Sternocleidomastoid
Scalene
Muscles of the shoulder girdle
– anterior seratti
– elevators of scapulae
– pectorals
Muscles of Expiration
Primary Muscles
The Diaphragm
Internal Intercostal Muscles
Accessory Muscles
Abdominal Muscles
– transversus thoracis
– transversus abdominis
– external obliques
– internal oblique
– rectus abdominis
Mechanics of pulmonary ventilation
The lungs can be expanded and contracted in two
ways:
1. By downward and upward movement of the
diaphragm to lengthen or shorten the chest cavity.
2. By elevation and depression of the ribs to increase or
decrease the antero-posterior diameter of the chest
cavity.
Normal quiet breathing is accomplished almost
entirely by the first method that is by movement of the
diaphragm.
Following events involved in a normal inspiration
Respiratory centers in the medulla oblongata
become active.
Signals are sent down the phrenic nerve to the
diaphragm and down the intercostal nerves to the
external intercostal muscles.
Diaphragm and external intercostals contract.
Volume of the thoracic cavity increases.
Lung volume increases.
Alveolar pressure decreases.
Air flows down the pressure gradient from the
atmosphere into the alveoli.
Inspiration continues until alveolar pressure =
atmospheric pressure.
Forceful inspiration
During forced inspiration accessory muscles
are involved so as to further increase thoracic
volume. Such muscles include:
– scalenes
– sternocleidomastoids
– shoulder girdle muscles
Contraction and expansion of the thoracic cage
Inspiration
Following events involved in a normal
expiration
Phrenic and intercostal nerves cease firing.
Diaphragm and external intercostals relax.
The thoracic volume decreases.
Lung volume decreases.
Alveolar pressure increases.
Air flows down the pressure gradient from
the alveoli into the atmosphere.
Expiration continues until the alveolar
pressure = atmospheric pressure.
Forceful expiration
Forced expiration differs in that muscles
contract in order to further reduce the size of
thoracic cavity.
Such muscles include:
–
–
–
–
–
transversus thoracis
transversus abdominis
external obliques
internal oblique
rectus abdominis
Expiration
Alveolar pressure, pleural pressure and
transpulmonary pressure
Changes in lung volume, alveolar pressure, pleural
pressure and transpulmonary pressure
Pressure changes throughout the respiratory cycle
Changes in lung volume, alveolar pressure, pleural
pressure and transpulmonary pressure
Valsalva Manoeuvre:
Valsalva manoeuvre refers to a forced expiration
against a closed glottis.
This causes marked decrease in the thoracic volume
causing deflation of lungs. Under such circumstances
the intrapleural pressure can become positive by 6070 mmHg.
The common everyday activities in which Valsalva
manoeuvre effect is seen in straining during
defecation, initial phase of coughing, during
parturition.
Muller’s Manoeuve:
Muller’s manoeuvre refers to
inspiration against closed glottis. It
reverse of the Valsalva manoeuvre,
reduces the intrapleural pressure up
mmHg.
forced
is just
i.e., it
to -80
Factors Affecting Pulmonary Ventilation
Elastic recoil of the lung
Surface tension
Compliance
Airway resistance
Elastic recoil of the lung
Elastic behaviour of the lungs depends upon its
collagen and elastic fiber.
Elastic behaviour of the lungs depends upon its
geometric arrangements (nylon shock
arrangement).
It also depends on the surface tension at the
air-liquid interface.
Surface tension forces a generated even
interfaces between two immiscible liquids.
They are generated by the cohesive forces
between the molecules of the liquid.
What is surface tension?
x
x
Therefore,
1. Larger alveoli have low collapsing pressure &
2. Smaller alveoli have high collapsing pressure.
Surface tension tends to produce collapse of
the alveoli.
But, two factors are responsible for not
collapsing of alveoli:
1. Pulmonary surfactant
2. Structural interdependence of alveoli make
the alveoli more stable
Surfactant
This high surface tension can lead to alveolar
collapse.
Collapsed alveoli require large amounts of
energy to inflate during inspiration.
Luckily, the type II alveolar cells produce the
chemical surfactant.
Surfactant decreases the cohesiveness of the
water molecules lining the alveoli and thus,
reduces alveolar surface tension.
x
x
Importance of Surfactant
1.
2.
3.
4.
5.
Reduces surface tension, therefore
increases compliance
Prevention of alveolar collapse
Stability of alveoli
Expansion of lungs at birth
Helps keep alveoli dry; helps prevent
pulmonary edema
Infant Respiratory Distress Syndrome
Surfactant production is inadequate until
the last 2 months of fetal development.
Thus, premature babies may suffer from
infant respiratory distress syndrome,
where the lack of surfactant leads to
alveolar collapse and tremendous difficulty
breathing.
Structural Interdependence of Alveoli
All alveoli are surrounded by other alveoli &
therefore supported by each other.
In a structure having connecting links like this,
any tendency for any one unit to expand or
contract is opposed by others.
Compliance
Compliance is the measure of distensibility of lungs.
The ease with which the lungs can expand facilitates
efficient ventilation.
Compliance of normal human lung is 200
ml/cm.H2O.
Replacement of the elastic lung tissue with non
elastic scar tissue as well as reduced surfactant
production will decrease lung compliance.
Inflation of lungs (inspiration) follows a different
curve than deflation of the lung (expiration); this
difference is called hysteresis.
Measurement of compliance
Comparison of the compliance diagrams of
saline-filled and air-filled lungs
Factors influencing lung compliance
Factors which decrease lung compliance
1. Disease that destroy lung tissue
2. Decreased distensibility of fibrotic tissue
3. Raised pulmonary venous pressure
4. Chest deformities & paralysis of respiratory muscle
Factors which increase lung compliance
1. Greater size of lungs
2. Increased age (because of alteration in elastic
tissue fibers of lungs)
3. Emphysema
Clinical significance
Low compliance: Indicating stiff lung, means more
work is required to bring in a normal volume of air.
Very high compliance: Lungs of patients with
emphysema have a high compliance and are
extremely easy to inflate.
Lungs with abnormally high compliance have poor
elastic recoil.
Thus, a lung affected by emphysema is easily
distended but does not recoil back during expiration.
Consequently, a lot of effort is required to get air out of
the lungs and looks “baggy”.
Thus, smoking-induced emphysema can lead to a
“baggy-lungs” that retain air.
Airway resistance
It is the resistance the air encounters while passing
through the airways.
It is explained by the following equation (Poiseuille's
law):
Where, R = Resistance, η = Viscosity, l = Length of
the tube, r = Radius of the tube.
Therefore, resistance will increase when there is:
(i) Decreased radii of the air passages,
(ii) Increased length of the passage and
(iii) Increased viscosity of the air.
The reverse conditions will decrease the resistance.
As such, the viscosity of air and the length of
the passage do not change.
So, the resistance is mainly dependent on the
radius of the airways.
The major site of airway resistance is the
medium-sized bronchi.
The smallest airways would seem to offer the
highest resistance, but they do not because of
their parallel arrangement.
Factors determining airway resistance
Lung volume: Less resistance when lung volume is
bigger; more resistance when lung volume is
smaller.
Contraction of smooth muscle: Contraction of
smooth muscle increases airway resistance. This by
irritants and by vagal stimulation. Sympathetic
stimulation
and
adrenaline
relax
bronchial
musculature via beta-adrenergic receptors.
Viscosity or density of the inspired air: It depends
on the density of the air. So, in compressed air
(deep-sea diving), the resistance is more and
resistance is low in high altitude.
Dynamic compression of airways
Expiration is normally a passive process.
Forced expiration increases the intrapleural and thus
alveolar pressure, increasing the pressure gradient to
the mouth and therefore theoretically leading to
increased flow.
Forced expiration from fully inflated lungs is effort
dependent.
Towards the end of the breath increasing force does
not increase flow, i.e. it is effort independent.
This occurs as a result of the pressure gradient
between the alveoli and the mouth.
Midway between them, generally in the bronchi, the
pressure in the airway falls below the intrapleural
pressure causing the airway collapse.
Thus the dynamic compression occurs.
As there is now no flow, the pressure rises again until
it is greater than the intrapleural pressure, and the
airway reopens.
This sequence happens repeatedly, producing the
brassy sound heard during forced expiration.
This does not occur in normal expiration because the
intrapleural pressure remains negative throughout.
In diseases in which the airways are already narrowed
(e.g. asthma), this leads to expiratory wheezing and
air trapping.
Work of breathing
Compliance work: Work which is required to expand
the lungs against its elastic forces.
Tissue resistance work: Required to overcome the
viscosity of the lung and chest wall structure.
Airway resistance work: Required to overcome the
resistance to the airflow.
During normal breathing, only 3 – 5% of the total
energy is required for pulmonary ventilation.
Factors which increase work of breathing:
1. Structural changes in lung and thorax.
2. Loss of surfactant.
3. Increased airway resistance.
Three different types of work done during inspiration
Spirometer
Spirogram
Lung Volumes
Tidal volume (VT) = 500 ml.
Inspiratory Reserve Volume (IRV) = 3000 ml.
Expiratory Reserve Volume (ERV) = 1100 ml.
Residual Volume (RS) = 1200 ml.
Lung Capacities
Inspiratory Capacity (IC) = 3500 ml.
Functional Residual Capacity (FRC) = 2300 ml.
Vital Capacity (VC) = 4600 ml.
Total Lung Capacity (TLC) = 5800 ml.
All lung volume & capacities are 20-25% less in
female than male; greater in large & athletic person.
Significance of Vital Capacity
Average vital capacity in young adult male of is about
4.6 L and in female 3.2 L.
The major factors that affect VC are:
1. Position of the person during measurement
(standing>sitting>lying)
2. Strength of respiratory muscle
3. Distensibility of the lungs and chest wall
(compliance)
4. Pulmonary congestion
Significance of Residual Volume
It provides air in the alveoli to aerate the blood
even between breaths.
It prevents marked fluctuation in the
composition of alveolar air.
It prevents the complete collapse of lung.
FRC and RV can not be measured with a
simple spirometer. Therefore, an indirect
method such as helium dilution method is
used to measure FRC.
RV = FRC-ERV and TLC = FRC+IC
Measurement of FRC
Helium-Dilution Technique:
Helium poorly soluble in water and thus diffuses very
poorly across the alveolar wall. Subjects breath a gas
that cannot escape from the lungs.
After several minutes of breathing, the helium
concentrations in the spirometer and lung become the
same.
From the law of conservation of matter, we know that
the total amount of helium before and after is the
same.
FUNCTIONAL RESIDUAL CAPACITY
• Helium dilution
• Spirometer of known
volume and helium
concentration connected
to the patient
At beginning
• Closed circuit
• Law of conservation of
mass
RV = FRC - ERV and TLC = FRC + IC
After several minutes
Anatomical dead space
TV is distributed between the conducting zone and
alveoli.
Since the gas exchange occurs only in the alveoli and
not in the conducting zone, part of the tidal volume
becomes wasted air.
This volume of air is known as dead space volume.
The normal dead space volume in a young adult man
is about 150 ml but increases slightly with age.
Tidal volume
= 500 ml
Dead space volume = 150 ml
Fresh air entering alveoli = 350ml
Physiological dead space
If areas of the lung do not function well they add to
dead space.
Physiological dead space is equal to Anatomical dead
space plus Alveolar dead space.
Physiological VD = Anatomical VD + Alveolar VD.
Alveolar dead space is the volume of air that enters
unperfused alveoli per minute. No gas exchange in
these alveoli.
For example:
● Alveoli not perfused by blood (pulmonary embolism)
● Collapsed alveoli (atelectasis)
● Damaged alveoli (smoking related emphysema)
Pulmonary ventilation or Minute ventilation
= Tidal volume (VT) x Respiratory Rate (R.R.)
= 0.5 L x 12 breaths/min
= 6 L/min.
Alveolar ventilation
= (VT – VD) x R.R.
= (500-150) x 12
= 350 x 12
= 4.2 L/min.
Ventilation – Perfusion Ratio
Normal alveolar ventilation (V) is 4.0 L/min and the
normal blood flow through the alveolar capillaries or
perfusion (Q) is about 5.0 L/min.
Thus the normal ventilation-perfusion ratio is equal to
0.8 (V/Q = 4/5 = 0.8).
In upright position, blood flow is decreased much more
than the ventilation. Therefore, at the top of the lung
V/Q ratio is about 3.3.
At the bottom of the lung, V/Q ratio is less (0.6).
Ventilation-Perfusion Relationship in the Lung
Ventilation- Perfusion Mismatching
Basic Properties of Gases
Air is made up of 79% nitrogen, 21% oxygen, smaller
amounts of carbon dioxide (0.04%) and water vapor,
and minute amounts of other gases.
The pressure exerted by atmospheric air is a sum of
the pressures exerted by each individual gas in the
air.
Thus each gas in a mixture of gases exerts a certain
amount of pressure. This is known as the partial
pressure for that gas.
Individual gases tend to move from one place to
another based on their partial pressure gradient.
Partial Pressures of Respiratory Gases
Gas Atmospheric Alveolar
Air
Air
Expired
Air
O2
CO2
H2O
N2
120
27
47
566
159
0.3
3.7
597
104
40
47
569
Arterial
Blood
95
40
47
573
Difference between the composition of
alveolar air and the atmospheric air
O2 is constantly removed from alveolar air
CO2 is constantly added to alveolar air
Only a small amount of fresh atmospheric air (350
ml) is added to the alveolar air (2200 ml; FRC)
Atmospheric air is humidified by the upper
respiratory passages before it enters alveoli.
Respiratory Membrane
•
•
•
•
Gas exchange between alveolar air and pulmonary
blood occurs through the blood-gas barrier called
respiratory membrane.
Total area of respiratory membrane about 70 square
meters.
The thickness of this membrane does not exceed
0.6 m.
It is composed of 6 layers:
1) A thin layer of fluid (surfactant and water)
2) Alveolar wall (simple squamous epithelium)
3) Basement membrane of alveolar wall
4) Interstitial space (between 3 and 5 layers)
5) Basement membrane of capillary wall
6) Capillary wall (capillary endothelium)
Respiratory Membrane
DIFFUSION ACROSS THE RESPIRATORY MEMBRANE
The amount of gas transferred is proportional to:
Surface area (A)
Diffusion constant (D)
Difference in partial pressure (P1 –P2), and
Thickness of respiratory membrane (T)
The constant (D) is proportional to gas solubility, but
inversely proportional to the square root of its molecular
weight (MW).
V gas  AD (P1 –P2)
D S
T
MW
Solubility of CO2 in normal saline at 370C is approximately 24
times greater than that of O2.
The diffusion rate of CO2 through a tissue sheet is about 20
times that of O2
Factors affecting net gas diffusion
through respiratory membrane
O2
CO2
Area
P2
P1
Thickness
Gas Exchange
● The partial pressure of O2 in the alveoli is 104 mmHg. The partial pressure of
O2 in blood entering pulmonary capillaries is 40 mmHg.
● The partial pressure of CO2 in the alveoli is 40 mmHg. The partial pressure
of CO2 in blood entering the pulmonary capillaries is 45 mmHg.
● At the systemic tissues the situation is somewhat reversed. Arterial blood PO2
is 95 mmHg while tissue PO2 is less than 40 mmHg.
● Arterial blood PCO2 is 40 mmHg while tissue PCO2 is greater than 45 mmHg.
● Notice that the partial pressure gradients for CO2 are much smaller than the
partial pressure gradients for O2.
CO2 does not require such a big gradient because it is much more soluble in
water; thus it enters the plasma much more readily than does O2.
Oxygen exchange through alveolocapillary
membrane
Diffusion of oxygen from tissue capillary to
the cells
Diffusion of carbon dioxide from pulmonary
blood into the alveolus
Uptake of carbon dioxide by the blood in
the tissue capillaries
Concept of Physiological Shunt
Shunt means alternative pathway. Blood, if bypasses the
pulmonary capillaries and is not oxygenated, called shunted
blood.
Therefore, a physiological shunt is the mixing of deoxygenated
blood with oxygenated blood.
Normally, about 2% of cardiac output passing through bronchial
vessels, rather than alveolar capillaries, is remain
unoxygenated (shunted blood from right to left side).
Perfusion of collapsed alveoli (atelectasis) will result in no gas
exchange and that blood will mix with pulmonary capillary
blood.
Thebessian circulation conveys blood from myocardium and
empties directly into the heart chambers without passing
through the lung.
Transport of Oxygen by Blood
O2 is carried by blood in 2 ways:
1. 3% of the O2 is simply dissolved in plasma.
2. 97% is bound to hemoglobin within RBC.
– Each Hb molecule can combine with up to 4 oxygen
molecules. [Hb4+4O2
Hb4 (O2)4].
– Hemoglobin with bound O2 is oxyhemoglobin.
– Hemoglobin without bound O2 is deoxyhemoglobin.
– Loading and unloading of O2 is given by a single
reversible equation: HHb + O2 ↔ HbO2 + H+.
Contd…
–
–
–
–
–
When Hb has 4 O2 molecules bound to it, it is
saturated.
When Hb has less than 4 O2 molecules bound
to it, it is unsaturated.
Note that in the lungs (where Po2 is 104
mmHg), Hb is fully saturated.
In the tissues (where Po2 is 40 mmHg), Hb is
75% saturated.
That means, on average, each Hb molecule
has 3 molecules of O2 bound to it.
Transport of Oxygen by Blood
O2 content of blood & transport from blood to
tissue
Arterial blood at Po2 = 95 mmHg, Hb is 97% saturated
& contains about 19.4 ml O2/100 ml.
Venous blood at Po2 = 40 mmHg, Hb is 75% saturated
& contains about 14.4 ml O2/100 ml.
Thus, 19.4 - 14.4 = 5 ml of O2/100 ml blood is
released from Hb and transported to the tissue.
Therefore, with normal cardiac output of 5 L/min,
250 ml of O2 is delivered to the tissues per minute
(5x5000/100).
Oxygen-hemoglobin dissociation curve
The curve is S – shaped or sigmoid shaped.
At alveolar Po2 of 104 mm Hg, Hb is 100% saturated
At arterial blood Po2 of 95 mm Hg, Hb is 97%
saturated.
When alveolar Po2 is decreased to as low as 60 mm
Hg, Hb is still 90% saturated.
This property of Hb ensures fairly high uptake of O2 by
blood even when alveolar Po2 is moderately
decreased.
The middle & lower parts of the O2- Hb dissociation
curve are concerned with O2 delivery to the tissue.
At Po2 of 40 mm Hg, Hb is 75% saturated with O2.
At this point, O2- Hb dissociation curve is very steep.
This means, in a small decrease in Po2 can result
substantial further dissociation of O2 for tissue use.
At Po2 of 20 mm Hg, Hb is 20% saturated with O2. The
total O2 content is only 4.4 ml/100 ml blood.
Concept of P50 and its significance
P50 refers to the partial pressure of O2 that produces a
50% saturation of the Hb with O2.
Normal P50 for arterial blood is 25-27 mm Hg.
Decreased P50 indicates increased affinity of Hb for
O2. Thus, decreased P50 is equivalent to shift of Hb-O2
curve to left. Fetal Hb and myoglobin has lower P50
value than adult Hb.
Increased P50 indicates decreased affinity of Hb for
O2. Thus, increased P50 is equivalent to shift of Hb-O2
curve to right. Increase in PCO2, H+ concentration,
temperature, and 2,3-DPG causes increased P50.
Concept of P50
Factors affecting oxygen-hemoglobin
dissociation curve
– Increased temperature in skeletal muscles due to
more heat production,
– Increased PCO2 due to accumulation of CO2
resulting from rapid metabolism,
– Decreased PO2 due to rapid consumption,
– Increased H+ due to more production of CO2 and
– Decreased pH due to accumulation of lactic acid
produced in muscular exercise.
– Increased 2,3-DPG due to anaerobic metabolism.
Effect of pH
Effect of PCO2
Effect of temperature
Effect of 2,3-diphosphoglycerate
The RBC are rich in 2,3-DPG which is formed from 3phosphoglyceraldehyde produce during glycolysis.
The 2,3-DPG is a highly charged anion that binds to
β–chain of deoxygenated adult haemoglobin.
HbO2 + 2,3-DPG
Hb. 2,3-DPG + O2
Thus, an increase in the concentration of 2,3-DPG
decreases the affinity of Hb for O2 and shifts the
normal O2-Hb dissociation curve to the right.
Causes of increased level of 2,3-DPG are anaemia,
exposure to chronic hypoxia at high altitude and
certain pulmonary diseases.
Effect of 2,3-DPG
Bohr Effect
A rise in PCO2 or a decrease in pH decreases the
binding affinity of Hb for O2 and hence shifts the O2-Hb
dissociation curve to the right.
The significance of Bohr effect lies in the fact that it
increases oxygenation of the blood in the lungs and
also increases the release of O2 from the blood in the
tissues.
Other Factors Affecting Oxygen Transport
Exercise: Production of larger amount of CO2, heat
and acids that will shift the curve to the right side.
Carbon Monoxide (CO): Toxic CO has 200-250 times
more binding affinity than O2. They shift the curve
towards left.
Fetal hemoglobin: HbF shift the curve to the left. HbF
has higher affinity for O2 than HbA promotes transport
of O2 across the placenta even at lower PO2.
Myoglobin: Mb, a heme protein that occurs in muscle
cells, consists of a single polypeptide chain attached
to a heme group. Therefore it can bind to a single
molecule of O2. The curve is towards the left.
Carbon monoxide poisoning
How would this affect O2 transport?
Carbon monoxide binds to hemoglobin
(carboxyhemoglobin) in the same binding site
as oxygen, but binds far more tightly (binding
affinity 200-250 times greater than O2).
It shifts the Hb-O2 curve to the left. Thus CO
prevent the loading of O2 into the blood in the
lungs and also interfere with unloading of O2
at the tissues. This is second deleterious
effect.
Carbon monoxide -hemoglobin
dissociation curve
Comparison of oxygen & carbon monoxide hemoglobin dissociation curve
Comparison of the O2-Hb dissociation curves
for HbA & HbF
Dissociation curves for HbA and Mb
Transport of CO2 by Blood
Transported primarily in 3 ways:
Dissolved in plasma (7%)
Bound to hemoglobin (23%)
–
–
–
In the plasma, CO2 combines with amino group of plasma proteins to
form carbamino proteins.
In the RBC, CO2 combines with amino group of hemoglobin.
Hb + CO2 ↔ HbCO2. HbCO2 is known as carbaminohemoglobin.
As bicarbonate ion in plasma (70%)
–
–
–
When CO2 diffuses out of the tissue fluid, it enters the plasma and then
the RBC. Within the RBC, CO2 combines with water to form carbonic
acid, which dissociates into a bicarbonate ion and a hydrogen ion.
The equation that describes what happens at the RBC in the tissues is:
CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+.
This reaction is catalyzed by the enzyme carbonic anhydrase.
Transport of CO2 by Blood
Chloride shift
As carbonic acid (H2CO3) is formed, it readily
dissociates to H+ and HCO3- ions.
HCO3- ions diffuse out of RBC in exchange for
chloride (Cl-) diffusion into the cell to maintain
electrical neutrality.
The Cl- movement is known as the chloride shift.
The Carbon Dioxide Dissociation Curve
The Carbon Dioxide Transport in the Blood
Venous blood at PCO2 = 45 mmHg contains about
52 ml CO2/100 ml of blood.
Arterial blood at PCO2 = 40 mmHg contains about
48 ml CO2/100 ml of blood.
Thus, 52-48 = 4 ml CO2/100 ml of blood is
transported from tissues to the blood to the lungs.
Haldane Effect
Binding of O2 with hemoglobin tends to
displace CO2 from the blood. This effect
called the Haldane effect.
In the lungs, it causes increased release
of CO2 because of O2 uptake by the
hemoglobin.
Respiratory Quotient
Normal transport of O2 from the lungs to the
tissue is 5 ml/100 ml of blood, whereas
transport of CO2 from the tissues to the lungs is
4 ml/100 ml of blood.
The ratio of CO2 output to O2 uptake is called
the respiratory exchange ratio or respiratory
quotient (R).
For a person on a normal diet the average
value for R is considered to be 0.8.
Respiratory acidosis
When plasma CO2 level increases (more than 45 mm
Hg), this in turn, increases the plasma H+ that leads to
a decrease in plasma pH.
If plasma pH drops below normal levels, we call it
respiratory acidosis.
Causes:
Respiratory depression/muscle paralysis, pulmonary
edema, pneumonia, asthma, anything causing
decrease in ability to ventilate.
Signs/Symptoms:
Breathlessness, restlessness, lethargy, disorientation,
muscle twitching, tremors, convulsions and coma.
Respiratory alkalosis
When plasma CO2 drops (below 35 mm Hg), this in
turn, decreases the plasma H+ that leads to an
increase in plasma pH.
If plasma pH rises above normal levels, we call it
respiratory alkalosis.
Causes:
Voluntary hyperventilation, hypoxemia, congestive
heart failure, hysteria, cirrhosis, improper use of
mechanical ventilation.
Signs/Symptoms:
Dizziness,
confusion, tingling
of extremities,
convulsions, coma, cerebral vasoconstriction.
Control of Respiration
Respiration is regulated by a complex integration of
neural control mechanisms which are modified by
chemoreceptors, lung receptors and inputs from
higher centers.
Neural control mechanisms:
● A system for automatic control of respiration as an
involuntary function. The involuntary control system of
respiration is located in the medullary and pontine
centers of the brainstem.
● Involuntary control which allows human to breathe
without conscious efforts under all circumstances
including sleep and is thus essential for life.
I. Neural control
The nervous system controls respiration by:
1. Respiratory center located in the brainstem
2. Higher centers
3. Respiratory reflexes
Respiratory center
The respiratory center is located bilaterally in the
medulla oblongata and pons.
It is divided into 4 major collections of neurons:
1. Dorsal respiratory group: Located in the dorsal
portion of the medulla
2. Ventral respiratory group: Located in the ventral part
of the medulla
3. Pneumotaxic center: Located dorsally in the superior
portion of the pons.
4. Apneustic center: Located in the lower part of the
pons.
Medullary Respiratory Centers
2 sets of neurons in the medulla oblongata are
the primary control centers.
1. Dorsal respiratory group (DRG)
2. Ventral respiratory group (VRG)
 Dorsal respiratory group (DRG)

● DRG are located bilaterally in the nucleus of the tractus
solitarius (NTS). NTS is the primary projection of visceral
afferent fibers of the IXth (glossopharyngeal) and Xth
(vagus) cranial nerves.
Stimulation of the DRG always causes inspiration, never
expiration.
Inputs to the DRG come from the vagus and
glossopharyngeal nerves.
The vagus nerve relays information from peripheral
chemoreceptors and mechanoreceptors in the lung.
The glossopharyngeal nerve relays information from
peripheral chemoreceptors.
Outputs from the DRG travel via the phrenic nerve to
the diaphragm.
Organization of the respiratory center
Genesis of rhythm of inspiratory signal
The inspiratory neurons initiate the inspiratory signals
to the diaphragm and other inspiratory muscles, which
contract.
The increase in inspiratory signals last for about 2
seconds and then stops for about 3 seconds in normal
respiration. The entire cycle repeats again.
The expiratory neurons remain inactive during normal
quiet respiration, because inspiration is achieved by
contraction of inspiratory muscles, while expiration
results from passive recoil of elastic structures of the
lungs and the chest cage.
When the respiratory drive for increased ventilation is
great, the expiratory center becomes active and
impulses go to the expiratory muscles, which
contribute their powerful contractile forces to the
respiratory process.
Ventral respiratory group (VRG)
–
–
–
–
–
The VRG are located bilaterally and the nucleus
are: the nucleus ambiguus and the nucleus
retroambiguus.
Involved in forced inspiration and forced
expiration.
They consist of both inspiratory and expiratory
neurons.
The neurons of the VRG remain almost totally
inactive during normal quiet respiration.
Their major function is to drive either spinal
neurons innervating mainly the intercostal and
abdominal muscles, or accessory muscles of
respiration innervated by the vagus nerve.
Secondary control centers: Pons.
Pneumotaxic center: Located dorsally in the nucleus
parabrachialis of the upper pons.
It transmits signals to the inspiratory area.
The primary effect of this center is to control the
"switch-off" point of the inspiratory ramp, thus
controlling the duration of the filling phase of the lung
cycle.
A pneumotaxic center limits the duration of inspiration
and increases the respiratory rate.
A strong pneumotaxic signal can increase the rate of
breathing to 30 to 40 breaths per minute.
A weak pneumotaxic signal may reduce the rate to
only 3 to 5 breaths per minute.
Apneustic center
Apneustic center is located in the lower portion of the
pons.
This center transmits signals to the inspiratory area in
an attempt to prevent turn off of the inspiratory signals.
This increases the tidal volume and duration of
inspiration.
Thus it also helps to adjust respiratory rate and depth
of respiration.
It gets feedback from the vagal afferents and also from
other respiratory centers.
As long as the pneumotaxic center is active, it
overrides the apneustic center.
Higher centers
Cerebral cortex, hypothalamus, and other parts of the limbic
system can also influence respiration. The higher centers may
control respiration in two possible ways:
(1) This control may bypass the respiratory centers completely,
using pyramidal fibers that innervate the same lower motor
neurons controlled by the DRG and VRG, and
(2) Higher centers may have an inhibitory or stimulatory effect
on the respiratory centers.
Breathing can be under voluntary control through cerebral
cortex; therefore, a person can voluntarily hyperventilate or
hypoventilate (breath-holding).
The voluntary control system facilitates acts like talking,
singing, swimming, etc.
Limbic system can alter the pattern of breathing in emotional
states such as rage and fear.
Hypothalamus can modulate respiratory pattern during pain.
Respiratory reflexes
The respiratory rhythm is altered reflexly not
only in response to metabolic signals but also in
response to proprioceptive and irritant stimuli.
These receptors are protective and operate on
exposure to toxic vapors, chemical irritants,
excessive lung inflation, or mechanical
stimulation of the respiratory tract.
Some of the better known respiratory reflexes
are described here.
(a) Hering-Breuer reflexes
There are two reflexes involved: inflation reflex and deflation
reflex. This reflex does not play a role in normal quite
respiration.
Hering-Breuer inflation reflex
Located in the smooth muscles of the airways throughout the
lungs.
These are stretch receptors that transmit signals through the
vagi into the DRG neurons when the lungs become
overstretched.
These signals affect inspiration in much the same way as
signals from the pneumotaxic center, i.e., they limit the duration
of respiration.
Therefore, when the lungs become overly inflated, the stretch
receptors activate an appropriate feedback response that
“switches off” the respiratory ramp and thus limits further
inspiration.
This is called Hering-Breuer inflation reflex. This reflex also
increases the rate of inspiration because of the reduced period
of inspiration.
Hering-Breuer deflation reflex
This reflex inhibits the expiratory center and
stimulates the inspiratory center when the lungs
are collapsing.
The receptors, which are distinct from those of
inflation reflex, are located in the alveolar wall
near the alveolar capillary network.
The smaller the volume of the lungs, the greater
the degree of inhibition, until expiration stops
and inspiration begins.
This reflex normally functions only during forced
expiration, when both the inspiratory and
expiratory centers are active.
(b) Irritation reflexes (sneezing & coughing)
Irritant receptors are located between the airway
epithelial cells in the trachea, major airways, and also
intrapulmonary airways.
The highest concentration of irritant receptors is in the
larynx and at the point where the trachea divides into
bronchi, called carina.
Irritant receptors are naturally stimulated by cold air,
mucus, dust, and any other particulate stimuli that
might reach the airways.
Information from the irritant receptors is conveyed to
the CNS by vagal afferent fibers.
It is possible that irritant receptors play a role in the
bronchoconstriction of asthma attacks as a result of
their response to the released histamine.
(c) J-Receptors
The term ‘’juxta-capillary,’’ or J, is used
because these receptors are believed to be in
the alveolar walls close to the capillaries.
J-receptors are stimulated when the pulmonary
capillaries become engorged with blood,
interstitial fluid volume increases or when
pulmonary edema occurs as in congestive
heart failure.
They may play a role in the rapid, shallow
breathing and dyspnea (sensation of difficulty
in breathing) associated with left heart failure
and interstitial lung disease.
(d) Joint and muscle receptors
Impulses from moving limbs are believed
to be part of the stimulus to ventilation
during exercise, especially in the early
stages.
Other Reflexes Affecting Respiration
Chemical control
The chemoreceptors are located in a chemosensitive
area near the ventral surface of the medulla near the
root of IXth and Xth cranial nerves.
This area is highly sensitive to changes in either blood
CO2 or H+.
This, in turn, excites the other portions of the
respiratory center.
Especially, it increases the activity of the inspiratory
center, which causes an increase in the respiratory
rate.
CO2 stimulates the chemosensitive area
Respiratory control by
Central Chemoreceptors
 CO2 in the plasma
 CO2 in the CSF
 H+ in the CSF
 CSF pH
Detected by the
medullary (central)
chemoreceptors.
Respiratory rate and
depth are adjusted.
85% of the respiratory
drive is mediated through
central chemoreceptors.
Central (medullary) Chemoreceptors
(Mechanisms: H+ & CO2 sensors)
Respiratory control by peripheral
chemoreceptors
The peripheral chemoreceptors which regulate
respiration are located in the carotid body and aortic
body.
These transmit nervous signals to the respiratory
center in the brain to help regulate respiration.
Both the carotid and aortic bodies monitor the levels of
PO2, PCO2, and H+ concentration in the arterial blood.
Approximately, 15% of the effect of respiratory drive is
mediated through peripheral chemoreceptors.
● Decreases in arterial PO2
The most potent natural stimulus for peripheral
chemoreceptors is low arterial PO2. When PO2 is less
than 60 mmHg, ventilation is exquisitely sensitive to
PO2.
● Increases in arterial PCO2
The response of the peripheral chemoreceptors to
PCO2 is less important than the response of the
central chemoreceptors to PCO2.
● Increases in arterial H+
Increase in arterial H+ stimulate the peripheral
chemoreceptors directly, independent of changes in
PCO2.
In metabolic acidosis, breathing rate increases
(hyperventilation) because of increased arterial H+ and
decreased pH.
Respiratory control by peripheral
chemoreceptors (carotid & aortic bodies)
Peripheral Chemoreceptors
Summary
of Chemoreceptor
Reflexes
A Summary of Chemoreceptor Reflexes
Over all
Regulation of
Respiration
Dorsal and
ventral
group of
neurons
Alteration in breathing pattern
Periodic breathing
An abnormality of breathing called periodic
breathing occurs in a number of disease
conditions.
The person breathes deeply for a short interval
of time and then breathes slightly or not at all
for an additional interval.
Thus the cycle repeats itself over and over
again.
Cheyne - Stokes breathing
The most common type of periodic breathing is
Cheyne-Stokes breathing.
Characterized by slowly waxing and waning
respiration.
It followed by apnea (lasting 10 to 30 seconds)
occurring over and over again every 45 seconds to 3
minutes.
Occurrence in disease
(a) Congestive heart failure and uremia: CheyneStokes breathing is commonly found in congestive
heart failure and uremia.
(b) Brain disease: It also occurs in patients with brain
disease.
Occurrence in healthy individuals
 Sleep
 High altitude
 Infancy
Causes
Cheyne-Stokes breathing is due to sluggishness of
chemical regulation of respiration.
Respiratory centers are depressed which do not
behave properly.
If stimulated there is over reaction.
The result is alternate apnea and hyperventilation.
Cheyne - stokes breathing
Biot’s Respiration:
Characterize by episodes of rapid uniformly
deep inspirations, followed by long periods (1030 seconds) of apnea.
Commonly seen in patients suffering from
meningitis, increased intracranial pressure,
severe brain damage etc.
Kussmaul breathing
The other name of this condition is acidotic breathing.
It occurs in case of metabolic acidosis as in diabetic
keto -acidosis, renal failure, etc.
The respiration is characterized by rapid and deep
breathing. This is due to stimulation by increased H+.
The main action of H+ of blood is via peripheral
chemoreceptors.
But H+ can also cross the blood brain barrier slowly
when the concentration is high and persistent.
In that case, the central chemoreceptors are
stimulated.
Its aim is to wash out CO2.
Kussmaul breathing
Common abnormal ventilatory patterns
Hyperventilation
When both the rate and depth of respiration are
increased the condition is called hyperventilation.
A combination of both causes the decreased PAco2
and Paco2.
Hypoventilation
When the alveolar ventilation is less than normal
caused by a decreased ventilatory rate and an
increased depth of breathing.
A combination of both causes increased PAco2 and
Paco2.
Hypercapnia
When CO2 content in the body increases the condition
is called hypercapnia.
It is mostly due to ventilatory failure or due to high CO2
in inspired air.
Asphyxia
It is a condition characterized by decreased oxygen
and increased carbon dioxide in the body.
Asphyxia = hypoxia + hypercapnia.
Orthopnea
The condition in which an individual is able to breath
comfortably only in upright position.
In the left ventricular failure the lungs are congested,
and therefore the patient may feel dyspneic.
The patient feels much better on standing up or sitting.
Hyperpnea
Hyperpnea is the general term for an increase in the
rate or depth of breathing.
Hyperpnea is normal immediately after exercise.
It is also associated with respiratory disease, infection,
cardiac disease, etc.
Tachypnea
It is rapid and shallow breathing.
Apnea
Apnea means absence of spontaneous breathing.
Apnea may last for more than 10 seconds.
Apnea occur in one third of normal individuals but frequent
among older men.
Occasional apneas occur during normal sleep.
Persons with sleep apnea the frequency and duration are
greatly increased.
1. Obstructive sleep apnea: caused by blockage of upper airway.
2. Central sleep apnea: occur when the neural drive to respiratory
muscles is abolished.
Other forms of apnea
1. Deglutition (deglutition apnea)
2. Breath holding (voluntary apnea)
Some important respiratory insufficiencies
Hypoxia
Hypoxia is a condition in which there is lack of O2 or
decreased O2 supply at tissue level.
Types
Depending on the cause, hypoxia is generally
divided into four categories1. Hypoxic hypoxia
2. Anemic hypoxia
3. Stagnant hypoxic
4. Histotoxic hypoxia
(1) Hypoxic hypoxia
It refers to the hypoxia that results from a low arterial
PO2.
There are a number of causes of hypoxic hypoxia, but
each result in lowering of the O2 content of the
systemic arterial blood.
The disorders which can lower the arterial PO2 are:
(a) Low alveolar PO2
Examples
This is quite common following ascent to high altitude
as the barometric pressure and PO2 falls with
increasing altitude.
(b) Reduced ventilation (Hypoventilation)
Examples
– Respiratory depression due to drug overdose (barbiturate
poisoning)
– Severe weakness of the muscles that support respiration
e.g. poliomyelitis, myasthenia gravis.
– Airway obstruction
(c) Reduced diffusing capacity
Examples
– Fibrosis of the lung parenchyma
– Pulmonary edema
(d) Low ventilation-perfusion ratio
(e) Arteriovenous shunt (physiologic shunt)
(2) Anemic hypoxia
This is due to a decrease in O2 carrying capacity of
blood.
It is caused by a decrease in the amount of
hemoglobin available for binding of O2 so that the O2
content of the arterial blood is abnormally low.
Examples:
Reduced erythropoiesis
Blood loss
Synthesis of abnormal hemoglobin
Carbon monoxide poisoning
(3) Stagnant hypoxia
If the blood flow through a tissue is sluggish. Blood
would stay in the capillaries for a longer time than
the normal.
The stay of blood in the capillaries may be so long
that even after extracting a very large fraction of O2
carried by the blood, all the requirements of the
tissue cannot be met. The result will be hypoxia.
Examples:
Reduced
cardiac
output:
cardiac
failure,
hemorrhage, circulatory shock
Embolism: slow or no circulation
Local vasoconstriction: exposure of the extremities
to the cold
(4) Histotoxic hypoxia
If the tissues are unable to use oxygen brought to
them by blood, even that results in hypoxia.
Histotoxic hypoxia refers to poisoning of the oxidative
enzymes of the cells.
In this situation the supply of O2 to the tissues is
normal but they are unable to make full use of it.
As a result the venous PO2 is abnormally high.
Examples:
– Cyanide poisoning
Effectiveness of O2 therapy in different
types of Hypoxia
Hypoxic hypoxia: Oxygen therapy is useful in all the
forms of hypoxia excepting shunts.
In atmospheric hypoxia, O2 therapy can completely
correct the decreased O2 level in arterial blood and
provide 100% effective therapy.
Even in the case of hypoventilation or low O2
diffusion in lung, breathing pure O2 can increase
transport of more O2 into the alveoli.
In shunts, admixture is after oxygenation in the lungs.
Hence oxygen therapy does not help.
Anemic hypoxia: O2 therapy has only slight value
because the amount of O2 transported by Hb can
hardly be increased. However, a small amount of extra
O2 can be transported in the dissolved state (7-30%).
Stagnant Hypoxia: O2 therapy is of very little value,
because the problem is slow blood flow and not
insufficient O2 .
Histotoxic Hypoxia: In this type of hypoxia, the tissue
metabolic enzyme system is simply incapable of using
the oxygen that is delivered. Therefore, oxygen
therapy has no measurable benefit.
Hyperbaric oxygen
Hyperbaric oxygen (high pressure oxygen) is specially
valuable in carbon monoxide poisoning.
It is also useful in the treatment of gas gangrene.
Since most of the hemoglobin is not available for
carrying oxygen, dissolved oxygen assumes special
importance for supplying oxygen to tissues.
The
solubility
of
oxygen
in
blood
is
0.003ml/100ml/mmHg.
Therefore if an arterial PO2 of 2000mmHg can be
achieved by administering 100% oxygen at a pressure
of 3 atmosphere, the blood will have 6ml/100ml
dissolved oxygen, which is adequate to meet the
metabolic requirements at rest.
Hyperbaric oxygen administered through a mask.
Dyspnea
Dyspnea is a subjective sensation of difficulty in
breathing.
The terms dyspnea, breathlessness, and shortness
of breath are often used interchangeably.
It is often associated with respiratory diseases, but it
can occur in healthy individuals also.
A common synonym is air hunger.
Dyspnea in disease
Dyspnea is observed in different cardiopulmonary
disease states:
(a) Primary lung diseases: Such as pneumonia,
asthma, and emphysema.
(b) Heart disease: Pulmonary edema.
(c) Neuromuscular disorders: Myasthenia gravis and
muscular dystrophy of the respiratory muscles.
Dyspnea in healthy individuals
(a) Exercise: In healthy individuals dyspnea occurs
during exercise, particularly in untrained individuals.
(b) High altitude: It is also common in subjects who
have rapidly climbed to a high altitude.
(c) Emotional or neurogenic dyspnea: In neurogenic
dyspnea or emotional dyspnea, the person's
respiratory functions may be normal and still dyspnea
may be experienced because of an abnormal state of
mind. This feeling is greatly enhanced in people who
have a psychological fear of not being able to receive
a sufficient quantity of air, such as in very small or
crowded rooms.
Causes
A person becomes very dyspneic especially from
excess build up of CO2 in the body fluids.
Dyspneic Index =
Where, MVV = Maximum voluntary ventilation.
PV = Pulmonary ventilation
Cyanosis
It is a clinical condition characterized by bluish discoloration of
the skin and mucus membrane.
Cyanosis is due to excessive amounts of deoxygenated
hemoglobin (HHb) in blood.
The amount of HHb in blood must be more than 5G/100ml.
Causes of Cyanosis
1. Asphyxia: Defective aeration of the lungs resulting in
impaired gas exchange, hypoxia and hypercapnia.
2. Hypoxia: Cyanosis is observed in hypoxic hypoxia and
stagnant hypoxia only.
Cyanosis does not occur in anemic hypoxia when the total Hb is
low. Cyanosis also does not occur in histotoxic hypoxia.
3. Cold: Cyanosis may occur when the blood flow through the
skin is reduced due to skin vasoconstriction by cold.
Types of cyanosis
Peripheral Cyanosis
Central Cyanosis
Peripheral cyanosis
Results from slow blood flow due to severe
vasoconstriction which produces stagnant circulation.
This can occur in peripheral circulatory failure resulting
in cold blue extremities.
More O2 is taken by the tissues and more HHb is
found. The peripheral cyanosis appears in the fingers
and toes.
Central cyanosis
Central cyanosis is mainly due to shunting of blood
from right to the left side bypassing the lungs as
occurs in congenital heart disease.
It also occurs in different lung diseases where
pulmonary gas exchange is affected. Due to
generalized causes, the central cyanosis appears in
all parts of the body. E.g. skin, mucous membrane,
tongue and nails of the hands.
Chronic obstructive pulmonary diseases (COPD)
The term chronic obstructive pulmonary disease
(COPD) denotes a group of respiratory disorders
characterized by small airway obstruction and
reduction in expiratory flow rate.
The most prevalent of these disorders are
emphysema, chronic bronchitis, asthma, etc.
Since the most common cause of COPD is smoking,
the disease is largely preventable.
In COPD, the time required for FVC is increased, the
FEV1.0 is decreased, and FEV1.0/FVC is decreased.
These are used in the diagnosis of COPD.
Emphysema
Emphysema is characterized by a loss of lung
elasticity and abnormal dilation of the air spaces distal
to the terminal bronchioles.
There is destruction of the alveolar walls and
hyperinflation of the lungs.
Breath sounds are decreased.
Types
There are two principal types of emphysemacentrilobular and panlobular.
(a) Centrilobular emphysema
Centrilobular emphysema affects the central or
proximal parts of the acinus, notably the respiratory
bronchioles.
(b) Panlobular emphysema
It involves the entire acinus from the respiratory
bronchioles to the alveolar sacs.
CENTRILOBULAR EMPHYSEMA
PANLOBULAR EMPHYSEMA
Causes
There are several known or suspected causes of
emphysema.
However, the most common causes are:
(1) cigarette smoking and inhalation of pollutants and
(2) deficiency of α1-antitrypsin
(1) Cigarette smoking and inhalation of pollutants
Inhalation of tobacco smoke is related to human
emphysema.
Among the many particulate and gaseous fractions to
be found in cigarette smoke are carbon dioxide,
nitrogenous
oxides,
sulphur
dioxide,
hydrocarbons, radioactive elements, phorbol
esters and, of particular interest relative to
emphysema, cadmium.
(2) Deficiency of α1-antitrypsin
α1-antitrypsin is a proteinase inhibitor.
It blocks the action of the proteolytic enzymes that are
destructive to elastin and other tissue components in
the alveolar wall.
The deficiency is an inherited autosomal recessive
disorder.
Chronic bronchitis
In chronic bronchitis, airway obstruction is caused by
inflammation of both major and small airways.
It is more common in men than in women, but
changing smoking habits may soon change this
disproportion.
It usually first appear in the fourth to fifth decades of
the life.
Causes
(1) Smoking and pollutants
(2) Infections: Viral and bacterial infections are the
common cause of the problem.
Asthma
Asthma is characterized by spastic contraction of the
bronchiolar smooth muscles, which causes extremely
difficult breathing.
It is a disease characterized by intermittent attacks of
dyspnea and wheezing caused by narrowing of the
bronchial airways.
The FRC and the RV of the lung become greatly
increased during the asthmatic attack because of the
difficulty in expiring air from the lungs.
Asthma occurs in 3 to 5% of the population at some
time in life.
Types and etiology
The usual cause of asthma is hypersensitivity of the
bronchioles to foreign substances in the air.
(1) Allergic hypersensitivity: In younger patients,
under the age of 30 years, the asthma in about 70% is
caused by allergic hypersensitivity, especially
sensitivity to some allergens.
(2) Nonallergic hypersensitivity: In older persons,
the cause is almost always hypersensitivity to
nonallergic types of irritants in the air, such as smog.
Lung Function Tests
Lung function tests are used to evaluate the
state of the respiratory system.
Lung function tests are useful to identify
patients with early airway disease.
By identifying disease at an early stage, its
progression can be slowed.
THE SPIROMETER
• Old version
– spirometer bell
– kymograph pen
• New version
– portable
1. Vital capacity (VC)
Maximum volume of air that can be expired after
maximum inspiration. It is measured by spirometer.
Normal value: 4.6 L in men
(20% less in women).
Major factors that affect vital capacity
– Posture (Standing>sitting>lying)
– Strength of respiratory muscle
– Distensibility of lungs and chest wall (compliance)
– Pulmonary congestion
2. Forced vital capacity (FVC)
Forced maximal expiration after maximal
inspiration.
It is measured by vitalograph.
Normal value equal to VC.
FVC and VC are measures of ventilatory
capacity.
Both values are reduced in:
– thoracic cage disease,
– paralysis of respiratory muscle,
– abnormalities of pleural cavity,
– pathology in lung itself.
3. Forced expiratory volume in first second (FEV1)
Volume of air expired by maximal effort in the first
second after a maximal inspiration.
Normal FEV1% = 75 - 80% of FVC.
FEV1% is affected by airway resistance during forced
expiration. It is reduced in:
i) Bronchoconstriction (asthma)
ii) Inhalation of irritant (cigarette smoking)
iii) Structural changes in the airway
iv) Obstruction within airway
FEV1% is reduced in obstructive lung diseases but
remains normal or increased in restrictive lung
diseases.
FEV1 & FVC
• Forced expiratory
volume in 1 second
– 4.0 L
• Forced vital capacity
– 5.0 L
• FEV1/FVC = 80%
4. Middle forced expiratory flow (FEF25-75 %)
FEF25-75% is the middle half volume of air in liters
divided by the time in seconds.
FEF25-75% and FEV1% is generally close in patients
with obstructive lung disease.
Normal value: 300 L / min.
5. Peak expiratory flow rate (PEFR)
Is the volume air expired in the first tenth of a second
(1/10th of a second) of a forced expiration after a
forced inspiration.
It is measured by Wright’s peak flow meter.
Normal value: 400-600 L / min.
6. Maximum Voluntary ventilation (MVV) or Maximum
breathing capacity (MBC)
It is the maximum rate of pulmonary ventilation that a
person can sustain for 15 seconds.
Normal value: 100 – 160 L / min in male;
60 – 100 L / min in female.
7. Residual volume (RV)
Volume of air left in the lungs after maximum
expiration.
Normal values:
20% of total lung capacity (TLC) at age of 20 yrs.
40% of TLC at age 60 yrs.
RV is increased in asthma, emphysema.
8. Compliance
Is the change in lung volume per unit change in
pressure (Δ V/Δ P).
Normal value: 0.2 L/cm H2O. Compliance is reduced
in pulmonary congestion and interstitial pulmonary
fibrosis. It is increased in emphysema.
9. Airway resistance
Is the pressure difference between the alveoli and
the mouth divided by the flow rate. Normal value: 1-3
cm H2O. It is moderately increased in bronchitis and
asthma.
10. Blood gases analysed
–
–
–
Arterial PO2
Arterial PCO2
Arterial blood pH