RESPIRATORY MODULE

1st MBBS Repeat Campaign - 2019

26TH BATCH 26TH BATCH – 2015/2016

26th Batch
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1st MBBS Repeat Campaign – 26th Batch

Mechanism of Inspiration and Expiration

Factors Needed for Efficient Functioning of the
Respiratory System Inspiration is an Active Process:
1. Diaphragm contracts – increases supero-inferior intrathoracic volume
1. Ventilation (V) 2. External Intercostals contract - pushes the sternum outward, upper
2. Perfusion (Q) ribs in a pump handle movement increasing the antero-posterior
diameter of the chest. Middle ribs move in a bucket handle motion,
3. V/Q Matching
increasing the transverse diameter.
4. Diffusion Across Alveolar-Capillary Membrane
3. Increase in intrathoracic volume
5. Gas Transport 4. The intra pleural pressure becomes more negative (-2.5 mmHg at the
6. Gas Exchange between capillaries & peripheral tissue base becomes -6 mmHg).
7. Regulation of Respiration 5. The lungs are pulled out and becomes more expanded
6. The pressure in the airways becomes slightly negative
7. Air flows into the airway via the gradient
❖ When considering any change in the respiratory system (e.g. NOTE: Accessory muscles of respiration =, such as the serratus anterior,
any disease/ disorder) consider how it affects ALL of the SCM, scalenus muscles, pec major, etc. also aid in an increased inspiratory
above. effort.
NOTE: The main function of the external intercostals is to prevent
paradoxical movement if the thoracic wall during inspiration (i.e. to
prevent the thoracic wall from collapsing when intrapleural pressure
decreases.
Ventilation
Quiet Expiration is a Passive Process:
• Ventilation is the movement of gas into and out of lungs through a 1. Diaphragm & External intercostals relax, reducing Intrathoracic
system of open airways along a pressure gradient. volume.
• During quiet respiration, expiratory period lasts twice as long as the 2. Intrapleural pressure becomes less negative.
inspiratory period. During exertion, time periods are nearly equal. 3. Lung recoils passively due to elasticity.
4. Alveolar pressure increases and becomes more than atmospheric
• The following factors affect ventilation:
pressure
1. Intact muscles of respiration & their innervation 5. Airflows out of the lungs
2. Lung Compliance
3. Airway Resistance
Forced Expiration is an Active Process
1. The events occurring in passive expiration also occur here.
2. Internal intercostals contract, pulling the ribcage down.
3. The Rectus Abdominis muscle contracts:
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1st MBBS Repeat Campaign – 26th Batch

a. Pulling the lower ribs back down
b. Increasing intraabdominal pressure which pushes the
diaphragm up
4. The above also actively aid in expiration.
Respiration in Lesions of the Nervous System
• Innervation of the diaphragm is by C3-C5 (mainly C4) nerve roots,
carried by the Phrenic nerve.
• Innervation of the external intercostals is by the T1-T11 nerve roots,
whose fibers pass along the intercostal nerves.
• In phrenic nerve damage, the dome on the same side of the
diaphragm is paralyzed, causing a characteristic increase in the
curvature of that dome (which decreases intrathoracic volume,
preventing lung expansion & impairing ventilation).
• If the spinal cord is transected above the C3 segment, it is fatal
without artificial respiration, since all inspiratory muscles (Diaphragm
& External Intercostals) are innervated by nerve roots below C3
• Transection below C5 segment is not fatal since the diaphragmatic
innervation is intact. The diaphragm is adequate to maintain sufficient
ventilation.
• Transmural Pressure = Alveolar Pressure – Intrapleural
Pressure:
o It is the positive, distending pressure that tends to
expand the lungs.
o Thus, it directly opposes elastic recoil.
o Since alveolar pressure is effectively zero, Tm pressure
at apex is 10 cmH2O, at the base it is 2.5 cmH2O.
o So, alveoli at the apex are more distended while those
at the base are less expanded, while at rest & standing.
o Thus, alveoli at the base can undergo more expansion
on inspiration, so they are better ventilated than those
at the apex (This difference is only present when
standing & disappears on lying down).
o Transmural pressure is also known as transpulmonary
pressure

Note on Lung Pressures

• Intra-alveolar pressure: -1 to +1 cm/H2O (0 at rest)

• Intrapleural pressure:
o It is the pressure of the pleural fluid outside the lung,
between the parietal & visceral layers of pleura.
o It is always negative due to the constant removal of
pleural fluid by the rich lymphatic drainage of the lung.
o At the base, it is less negative (-2.5 cmH2O) because of
gravity.
o At the apex, it is more negative (-10cmH2O)
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1st MBBS Repeat Campaign – 26th Batch

Lung Compliance • Compliance is increased in Emphysema and in old age. This requires
high deflating pressure.
• Compliance is the increase in lung volume per unit increase in
transmural pressure, given enough time to achieve equilibrium.
• Compliance is higher during deflation than in inflation of the lung. This
difference is mainly due to surfactant, which is secreted during
expiration to prevent lung collapse (see below).
• Lung Compliance Depends on the Following:
1. Total Lung Volume
2. Elastic Recoil of Lung Tissue
3. Elastic Recoil due to Surface Tension (and effect of
Surfactant)

Total Lung Volume

• Lung compliance is directly proportional to the total lung

volume. E.g. Compliance for both lungs is 200ml/cmH2O. If one
lung is removed, it decreases to 100ml/cmH2O.
• So, infants, who have smaller lungs have a lower lung
compliance, which may contribute to respiratory distress.
• Conversely, in people who have larger than normal lungs (e.g.
in athletes or due to high altitude), lung compliance is higher.

Elastic Recoil of Lung Tissue

• Elasticity is the ability to return to the original form/volume

upon stretching. Collagen & Elastin in the lung parenchyma
give it its elastic property.
• Lung compliance is inversely proportional to the amount of
elastic tissue
• Compliance is decreased in pulmonary fibrosis and pulmonary
oedema. This requires high inflation pressure.

1st MBBS Repeat Campaign – 26th Batch
Barrel shaped chest in Emphysema
• Chest and lungs have elastic property each pulling in opposite
direction:
o Chest wall is pulled outwards due to tone of external
intercostals
o Lungs are pulled inwards due to elastic forces
(parenchyma & surface tension)
• In Emphysema, alveolar septa which provides some of the recoil forces
in lung are destroyed & there is a loss of inward force by lungs.
• Also, airways are held open by elastic tissue during inspiration (radial
traction, see below). Loss of support during expiration causes airways
to collapse. This effect is increased in emphysema due to loss of elastic
tissue. Expiration is impaired, & the Functional Residual Capacity (FRC)
& total lung volume increases.
• Over a period of time due to increased total lung volume & the
unopposed outward force of the body wall, permanent enlargement
of thoracic cage occurs.
• This is known as barrel shaped chest.
*** Compliance is a static measure of lung and chest recoil.
4
Elastic Recoil Due to Surface Tension
• Walls of alveoli are lined with fluid. Hydrogen bonds between
water molecules of this fluid result in a strong molecular
attractive force that tends to collapse alveoli.
• Elastic recoil due to surface tension is greater than due to the
elasticity of lung parenchyma.
• The Law of Laplace can be applied to alveoli:
2𝑇
𝑇𝑟𝑎𝑛𝑠𝑚𝑢𝑟𝑎𝑙 𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒 =
𝑟
Where T = surface tension & r = alveolar radius
• Thus, the Law of Laplace denotes an equilibrium between the
opposing forces of transmural pressure (which expands
alveoli) & surface tension (which collapses alveoli).
• As the alveolar radius decreases (e.g. during expiration), surface
tension increases (Water molecules are closer together) & tends
to overcome the transmural pressure, which decreases (since
intrapleural pressure becomes less negative), thus causing
atelectasis.
Actions of Surfactant
• Surfactant is a mixture of dipalmitoyl phosphatidylcholine, other lipids
and proteins, secreted by Type ll alveolar epithelial cells
(pneumocytes)
• Maturation of these cells occur at 26-28 weeks of pregnancy.
• During this period, due to the activity of the feto-placental unit,
glucocorticoid synthesis increases in the foetus.
• Glucocorticoids accelerate maturation of type II pneumocytes, thus
promoting surfactant synthesis & lung maturity (ref. reproductive).
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1st MBBS Repeat Campaign – 26th Batch

• Surfactant lowers the surface tension of alveoli, by disrupting
attractive forces between water molecules.
• Surfactant is usually excreted during expiration to prevent lung
collapse.
• By lowering the surface tension, surfactant:
o Increases lung compliance
o Decreases work of breathing
o Prevents lung collapse
o Maintains alveolar stability
o prevents pulmonary edema.
• Surfactant production is impaired in Adult & Infantile Respiratory
Distress Syndrome, Septic Shock & Severe Pneumonia.
Role of Surfactant in maintaining Alveolar Stability & Preventing
Alveolar Collapse - the "Law of Laplace"
collapse, the radius is maintained, which prevents developing a
pressure gradient from smaller alveoli to larger ones. Thus, it
maintains alveolar stability.
Role of Surfactant in Preventing Pulmonary Oedema
• Surfactant lowers the surface tension of alveoli.
• This reduces inward force of lungs. Decreased elastance decreases the
pulmonary interstitial space volume
• According to Boyle's law PV = K
• Thus, pulmonary interstitial hydrostatic pressure becomes less
negative.
• This decreases the filtration across the pulmonary capillaries:

• Surfactant helps to keep the smaller alveoli open and prevents them
emptying into larger ones thus maintaining alveolar stability 7 28
P = 2T
R

P – Distending pressure Interstitial space 14 8

T – Surface tension
R – Radius 7 – Capillary Hydrostatic P
28 - COP
As P ∞ 1/R R P 14 - ISF Osmotic P
8 - IPP transmitted to ISF

• Smaller alveoli have a greater alveolar & thus distending transmural With surfactant Without surfactant
pressure. Capillary Hyd. P. 7 7
• Along the pressure gradient, smaller alveoli will empty into larger Interstitial On. P. 14 14
alveoli, so alveoli are unstable. Negative Hyd. P. 8 20
• Also, in smaller alveoli, surface tension is greater, which may cause Net Outward P. 29 41
alveolar collapse (atelectasis).
• Surfactant is released in smaller alveoli during expiration. It reduces Plasma On. P. 28 28
surface tension & prevents alveolar collapse. Since it prevents Net Inward P. 28 28
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1st MBBS Repeat Campaign – 26th Batch

Net Filtration +1 +13

• According to Starling’s forces,

(7+14+8) - 28 = +1 (net filtration force)
• The slight filtration is drained by the lymphatics
• In a Surfactant deficiency the net filtration force will become more
negative, exceeding the limit of lymphatic absorption
• Surfactant as stated above will prevent fluid accumulation in the
pulmonary interstitial space preventing pulmonary edema.
Airway resistance
• Airway resistance (R) is mainly due to friction of gas molecules with
each other and with the wall of airways.
• There is a minor role played by friction of lung tissue as the lung
volume changes.
• According to the Poiseuille-Hagen Formula,

Surfactant Therapy in Respiratory Distress Syndrome in the New- R = 8ɳl

Born Пr4

• Infant respiratory distress syndrome (IRDS) is the condition of a R – Resistance

newborn infant in which the lungs are imperfectly expanded.
• Initial inflation and normal expansion of lungs requires surfactant to
prevent alveolar collapse. Without surfactant the alveoli collapse,
leading to inefficient and “stiff" lungs causing difficulty in breathing.
• Maturation of surfactant secreting Type ll alveolar epithelial cells
occur at 26 -28 weeks of pregnancy. So IRDS is the most common and
serious among preterm infants in whose surfactant may be deficient.
• As treatment surfactant is administered. Surfactant lowers surface
tension. Glucocorticoids can also be administered to the mother to
promote surfactant secretion in utero.
• According to law of Laplace.
• P=2T/R as R reduces, Surfactant will reduce T. Thereby Y will not
exceed P
• In a surfactant deficiency state,
• As R reduced T> P lungs will collapse
• Thus, surfactant by lowering surface tension will prevent lung collapse
in IRDS.
ɳ - Viscosity
l – Length of the air way
r – Radius of the air way
• Small change in r affects the R greatly, if the r becomes 1/2, the R is
increased by 16-fold.
• 7th bronchial division has the highest R (medium sized bronchi).
• Radial friction forces pull the air way open and reduce the R.
• Flow = Diffusion pressure / Resistance
• Increased R causes increased pressure drop along the airway which
may lead to premature closure and air trapping.
• Airway resistance is increased in COPD (e.g. - Bronchial Asthma) which
requires greater inspiratory and expiratory forces to maintain normal
airflow rate
• Factors affecting Bronchial Radius & Airway radius are:
o Bronchomotor Tone
o Radial Traction

1st MBBS Repeat Campaign – 26th Batch
Bronchomotor Tone
Increase in airway resistance in bronchial asthma
• This is the tone of the bronchial smooth muscle.
• Parasympathetic innervation of bronchial smooth muscle is
via the vagus nerve. Nerve endings release Ach which act on
M3 (Muscarinic) receptors to cause Bronchoconstriction.
• Sympathetic innervation of bronchial smooth muscle releases
Norepinephrine which acts on β2 receptors to cause
Bronchodilatation & α1 receptors to cause inhibition of
bronchial secretions.
• Bronchi Dilate during inspiration & constricts during
expiration, via a stretch initiated vagal reflex – This makes
expiration more difficult than inspiration.
• Circadian rhythm affects bronchomotor tone: Maximum
constriction occurs early in the morning (eosinophil count is
also increased).
• Constriction via a Vagal reflex in response to irritants (e.g.
Cold air, dust, gases)
Radial Traction – Effect of Lung Volume on Airway resistance
Salbutamol treatment in an exacerbation of bronchial asthma
• Bronchiolar patency is maintained by elastic lung parenchyma.
• Radial Traction: During inspiration, as the lung expands, the
elastic tissue is stretched, this causes traction (pulling) on the
bronchioles which increase its diameter & reduces airway
resistance. The decreased intrathoracic pressure also facilitates
expansion of bronchioles.
• During expiration, elastic recoil & increased intrathoracic
pressure cause the bronchioles to collapse. This is another
reason expiration is more difficult, especially in emphysema.
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• Bronchial asthma is a chronic inflammatory disease in the bronchi
which leads to the airway narrowing.
• In bronchial asthma, exposure of allergens for the first time, produces
IgE which bind to receptors on the mast cell surface.
• During 2nd exposure of the same allergen, allergen binds to the specific
receptor on mast cell surface.
• This results in degranulation of mast cells & increased release of
histamine, prostaglandins, and leukotrienes.
• This causes contraction of bronchial smooth muscles
(Bronchoconstriction) & Vasodilation of blood vessels which supplies
mucous glands resulting in increased mucous secretion and mucous
plug formation
• Bronchi are infiltrated with leucocytes causing inflammation and
edema
• All of the above cause narrowing of the airway, reduced radius of the
airway. According to Poiseuille’s law, there is increased air way
resistance.
• Asthma is a (Type l hypersensitivity) chronic airway inflammatory
disorder which is characterized by episodic or chronic wheezing, cough
and a feeling of tightness in the chest as a result of
bronchoconstriction.
• Asthma causes fluid secretion into the lumen of the bronchi, and
deposition and secretion of mucous as well. This narrows the
bronchial lumen. Its further reduced by thickening of the bronchial
wall. This increases airway resistance.
• According to Poiseuille’s law, a small change in radius results in a 4-
fold change in resistance.
• In asthma patients due to narrowing of the airway the resistance is
greatly increased reducing airflow velocity.
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1st MBBS Repeat Campaign – 26th Batch

• Increase airway resistance cause breathlessness and tightness of chest

in asthma. In normal inspiration bronchi dilate due to reduced
pressure in lungs. In expiration with the increase in pressure
bronchioles constrict. They feel more difficulty in expiration.
• Bronchi are supplied by autonomic nervous system. The Sympathetic
system is responsible for bronchodilation through β2 receptors.
• Salbutamol is a β2 agonist. So, it is given as a treatment for bronchial
asthma
• Salbutamol, binds to β2 receptors in bronchi, relaxes bronchial smooth
muscles (bronchodilation), reduces bronchial secretions, thus
increases bronchial radius & reduces airway resistance
• Results in reduced breathlessness & work of breathing.

Summary of Ventilation

❖ Consider all of the above when dealing with a lung disorder.

Work of Breathing

• Work of breathing (WoB) is the energy expenditure incurred for

pulmonary ventilation, expressed in Kg m/min.
• Since inspiration is active & quiet expiration is passive WoB is
normally considered only for inspiration. But, in conditions
where expiration is forced & active, WoB is further increased.
• At rest WoB accounts for only 3% of total energy expenditure.
This increases greatly during exercise.
• WoB is increased in the following conditions:
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1st MBBS Repeat Campaign – 26th Batch

o Exercise
o Any disorder causing increased airway resistance (e.g.
Asthma, COPD)
o Any disorder causing decreased compliance (e.g.
Congestive Cardiac Failure causing Pulmonary Oedema)
• Respiratory muscles, like any other skeletal muscle, has a
length-tension relationship and can’t maximally contract when
they are severely stretched (e.g. Emphysema)
• Respiratory muscles can also become fatigued

Factors Affecting WoB

1. Work against elastic tissue of lungs and chest wall and surface
tension – 65%
2. Work against Airway resistance – 28%
3. Work done to move inelastic tissue (e.g. ribs) – 7%

1st MBBS Repeat Campaign – 26th Batch
Lung Volumes and Capacities
Lung Volumes
• Tidal Volume (TV) – Volume of air that is inspired or expired
during quiet breathing: 500-700ml
• Inspiratory Reserve Volume (IRV) – Volume of air that can be
maximally inspired more than the tidal volume: 3000ml
10
• Expiratory reserve Volume (ERV) – Volume of air that can be
maximally expired after quiet expiration: 1100ml
• Residual Volume (RV) – Volume of air that remains in the lung
after a maximum forceful expiration, corresponding to the
anatomical dead space: 1200ml
Lung Capacities
• Total Lung Capacity (TLC) – Maximum volume of air the lungs
can contain, i.e. the sum of vital capacity & residual volume:
5500ml
• Vital Capacity (VC) – Volume of air that can be maximally
expelled after a maximum inspiration. VC=IRV + TV + ERV:
4600ml
• Inspiratory Capacity (IC) – TV + IRV
• Functional Residual Capacity (FRC) – ERV + RV: 2300ml
• Respiratory Minute Volume (RMV)– The amount of new air
moved into the respiratory passages each minute:
RMV = TV × Respiratory Rate
= 500 × 12
= 6000ml/min
[Normal Respiratory Rate = 12-15/min]
Note: Total Alveolar Ventilation is less than RMV since Tidal
Volume includes the air entering the non-alveolar parts of the
respiratory tracts (i.e. the conducting passages or anatomical dead
space.
• Maximum Voluntary Ventilation (MVV) – Largest volume of gas
that can be moved into & out of the lungs in 1 minute by
voluntary effort: 125-170L/min
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1st MBBS Repeat Campaign – 26th Batch

Dead Spaces

Anatomical Dead Space Use of Lung Volumes/Capacities to Determine Lung

• Some of the inspired air never reaches the gas exchange areas
(i.e. alveoli) but fill the conducting passages. This is known as
the anatomical dead space where no gas exchange occurs.
• This correspond roughly to the weight of an individual in
pounds. i.e. in a 150lb man with a tidal volume of 500ml, only
350ml is involved in alveolar ventilation.
• On expiration, air in the dead space is removed first, only then
are the alveoli filled. Therefore, rapid shallow breathing
results in less ventilation than deep breaths.
Physiological Dead Space
Dysfunction
• Forced Vital Capacity (FVC) – This is the largest amount of air
that can be forcefully expired after a maximum inspiratory
effort: 4 L
• Forced Expiratory Volume in the 1st Second (FEV1) – This is the
fraction of the FVC expired during the 1st second of a a rapid,
forced expiration: 3.3 L
• FEV1/FVC Ratio is an important diagnostic tool in
differentiating Obstructive & Restrictive lung disorders.
• Normal FEV1/FVC ratio is around 83%.

• Air in some alveoli may not contribute to gas exchange,

therefore it is a dead space.
• In airway obstruction, since air is trapped in the alveoli,
diffusion of gases results in an equilibrium being reached such
that there is no further gas exchange (The trapped air is
gradually absorbed by the lung).
• Alternatively, the affected alveoli can be poorly perfused. Here
again an equilibrium is reached, and no further gas exchange
occurs.
• In a healthy individual, the physiological dead space is equal to
the anatomical dead space, since gas exchange occurs in all
ventilated alveoli.

1st MBBS Repeat Campaign – 26th Batch
Obstructive Disorder
Inspiration is mainly unaffected,
since the negative intrapleural
pressure, radial traction &
reduced bronchomotor tone
increase the airway patency; IRV
is unchanged
Expiration is greatly affected,
due to the increase in airway
resistance in expiration caused
by the increased intrapleural
pressure, elastic recoil of lung
parenchyma & increased
bronchomotor tone; airways are
almost completely blocked
FEV1 is greatly reduced, since
Flow=Pressure gradient/
Resistance, when resistance
increases, the flow rate
decreases so the air expired in 1
second reduces
FVC is reduced or unchanged.
Since inspiration can occur
normally, FVC may remain
unchanged in acute conditions.
However, in chronic conditions,
there is accumulation of air that
can’t be expired, leading to a
decrease in FVC
FEV1/FVC ratio<83%
Tidal Volume is unchanged
Residual Volume & FRC are
increased, since expiration is
impaired, with each breath,
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Restrictive Disorder some air is trapped in the lung.
Inspiration is affected since the With time air accumulated in the
lung expansion is impaired; IRV lung, which remains even after
is reduced forces expiration, i.e. RV is
increased
Total Lung Capacity is increased Total Lung Capacity is
due to the inability to expire air decreased due to failure of lung
Expiration is less affected since expansion
airway obstruction isn’t present E.g. Asthma, COPD E.g. Myasthenia Gravis,
Pulmonary Fibrosis, Obesity
❖ NOTE: In Obstructive disorders, as total lung capacity
progressively increases, the length-tension relationship of the
respiratory muscles is deranged & lung expansion is impaired,
which leads to a mixed disorder.
FEV1 is reduced, mainly because
the FVC is reduced due to the
decrease in IRV. Therefore, the
decrease in FEV1 is proportional
to the decrease in FVC.
FVC is reduced due to the failure
in lung expansion.
FEV1/FVC ratio> or = 83%
Tidal Volume is unchanged
Residual Volume & FRC remain
unchanged, since expiration can
occur normally
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1st MBBS Repeat Campaign – 26th Batch

Pulmonary Circulation 4. Capillary Hydrostatic Pressure (7mmHg) < Colloid Oncotic

• Lungs accommodate a large proportion of the total blood in the
body & acts as a reservoir system.
• Blood shifts from pulmonary circulation to systemic circulation
in response to blood loss/ hypovolemia.
• Blood shifts from systemic circulation to pulmonary circulation
in:
1. Left Ventricular Failure
2. Mitral Stenosis
3. Mitral Regurgitation
• Circulation of the lungs are of 2 types:
1. Bronchial Circulation – A high pressure, high resistance,
low flow system that carries oxygenated blood from the
aorta, to supply the lung parenchyma & conducting
airways. Drains into the pulmonary veins mainly,
although bronchial veins also drain into the azygos
system.
2. Pulmonary Circulation – Supplies deoxygenated blood
to the areas of the lung responsible for gas exchange.
Special Features of Pulmonary Circulation
Pressure (28mmHg). This is important to prevent pulmonary
edema (See below). In systemic circulation, it is vice versa.
5. Short Pathway – Blood flows from the right ventricle, through
the lungs, then to the left atrium.
Pressures of Pulmonary Circulation
1. Pulmonary Artery – 25/8mmHg
2. Pulmonary Veins – around 8mmHg
3. Right Atrium – 2mmHg (Left is greater, at 5mmHg)
4. Right Ventricle – 25/0mmHg
5. Pulmonary Capillary – 7mmHg
Shunting in Pulmonary Circulation
• Alveolar partial pressure of O2 (PAO2) is 100mmHg, but that of
arterial blood (PaO2) is 95mmHg.This is due to anatomical &
physiological shunting.
• In shunts, deoxygenated blood enters

1. High Flow – Equal to the Cardiac Output of 5 L/min, thus is the
organ that has the largest blood flow.
2. Low Pressures – BP is 25/8 mmHg, which is 1/6 of the systemic
pressure (MAP= DBP + 1/3 PP = 15mmHg)
3. Low Resistance – About 1/6 of the TPR of systemic circulation.
This is achieved by capillary dilatation & recruitment in
response to a change in blood flow. Also, Vessels are highly
compliant, allowing them to act as reservoirs.
Anatomical Shunts
1. Anastomosis between bronchial capillaries & pulmonary
capillaries or veins, results in deoxygenated blood entering the
left atrium & arterial blood (Bronchopulmonary Anastomosis).
2. Venae Cordis Minimae which drain into the left side of the
heart.

1st MBBS Repeat Campaign – 26th Batch
Physiological Shunting
• Capillaries which perfuse poorly ventilated alveoli don’t receive
O2
• This is since the alveolar PO2 has equilibrated with venous
blood, there is no partial pressure gradient along which O2 can
diffuse.
• Thus, the deoxygenated blood of these capillaries enters
pulmonary veins, diluting & decreasing the PaO2.
• This is termed physiological shunting, and, like physiological
dead spaces, this is abnormal.
Factors Affecting Pulmonary Blood Flow
1. Hydrostatic Pressure – The hydrostatic pressure of pulmonary
blood at the heart level is approximately the blood pressure in
the right ventricle.
a. Above the heart level, the hydrostatic pressure is less
b. Below the heart level, the hydrostatic pressure is more
2. Arterio-venous Pressure Difference of Pulmonary Vessels:
a. Pulmonary Arterial Pressure varies with the cardiac
cycle (25/8mmHg)
b. Venous Pressure remains relatively constant, due to
the high compliance of veins
3. Alveolar Air Pressure – This is the distending pressure of the
alveoli that tends to compress & reduce blood flow in
capillaries. It varies slightly with the respiratory cycle (+1 to -
1mmHg)
Accordingly, Pulmonary blood flow varies with the region of the
lung & can be classified into zones.
14
Zones/Patterns of Pulmonary Blood Flow
1. Zone 1: Zero Blood Flow
o Alveolar Air Pressure>Alveolar Capillary pressure
throughout the cardiac cycle.
o Only occurs in abnormal conditions such as excessive
blood loss.
2. Zone 2: Intermittent Blood Flow (Waterfall Effect)
o During Systole: Alveolar Capillary Pressure>Alveolar Air
Pressure, blood ‘falls’ into pulmonary veins.
o During Diastole: Alveolar Air Pressure>Alveolar
Capillary Pressure.
o This pattern of blood flow occurs from the lung apex to
10cm above the midpoint of the heart.
3. Zone 3: Continuous Blood Flow
o Alveolar Capillary Pressure>Alveolar Air Pressure
throughout the cardiac cycle, so blood flow is
continuous.
o This pattern of flow occurs in the lung base at rest (so
lung bases are better perfused than the apex).
o It also occurs throughout the during exercise.
Pulmonary Oedema
• It is the accumulation of fluid in the pulmonary interstitial
spaces.
• Normally, the net filtration pressure of pulmonary capillaries is
1mmHg, & the small amount of tissue fluid formed is removed
by lymphatics (See above).
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1st MBBS Repeat Campaign – 26th Batch

Causes of Pulmonary Oedema V/Q Ratio

1. Increased Capillary Hydrostatic Pressure: Due to Left
Ventricular Failure, mitral stenosis or regurgitation.
2. Increased Capillary Permeability: Due to infections, noxious
gases, etc.
3. Surfactant Deficiency: This increases the recoil tendency of the
lungs, increasing the negativity of the intrapleural pressure.
Pulmonary Oedema Safety Factor
• At the lung level, V is the total alveolar ventilation, Q is the
cardiac output.
• V=4.2 L/min, Q=5.2 L/min, so at rest, the V/Q ratio of the whole
lung is 0.8.
• Ideally, the ventilation (V) should be perfectly matched to the
perfusion (Q) for efficient gas exchange, so the ideal V/Q ratio is
1.0
• V/Q ratio balance is the major determinant of gas exchange. A
V/Q mismatch will affect O2 diffusion more.

• Normally, the capillary hydrostatic pressure of 7mmHg is

countered by the capillary colloid oncotic pressure of 28mmHg. Regional Variation of V/Q in Lung
• The safety factor is a phenomenon in which pulmonary edema
due to increased hydrostatic pressure doesn’t occur until the
Lung Region Ventilation Perfusion V/Q Ratio
hydrostatic pressure is equal to the colloid oncotic pressure.
(L/min) (L/min)
• Thus, the hydrostatic pressure must be increased by 3-fold
Apex 4 1.2 3.3
before edema occurs.
Middle 5 5 1.0
Base 6 10 0.8
Regulation of Pulmonary Circulation
❖ Both V & Q increase towards the base because of gravity
(Explain the changes described above).
1. Autoregulation: Unlike in systemic circulation, (Alveolar)
❖ However, the relative increase in perfusion is greater than
hypoxia, decrease in pH & increase in CO2 causes
ventilation, so V/Q ratio decreases.
vasoconstriction.
2. Autonomic Innervation – As in Systemic Circulation.
3. Humoral Agents – Histamine, Bradykinin & Endothelial NO
cause vasodilatation.
 16
1st MBBS Repeat Campaign – 26th Batch

Changes in V/Q Ratio o Alveolar PO2 & PCO2 tend to move towards
atmospheric values.
o Hypoxemia occurs
• Either an increase or a decrease in the V/Q ratio from normal
• Causes: Any cause of impaired prefusion of alveoli
(0.8) is abnormal & occurs in disease conditions.
• E.g. Pulmonary embolism, Interstitial Lung Disease,
• Both cases cause arterial Hypoxemia (PaO2 decreases).
Hypovolemic shock
Hypercapnia (Increased PaCO2) may also occur.
• NOTE: In lung collapse (atelectasis), collapse of alveoli decrease
ventilation but capillaries are also compressed, so there is a
V/Q Mismatches – Effect on Blood Gases
decrease in prefusion. As a result, changes in V/Q are mild and
hypoxemia is also mild.
1. Total blood O2 content is reduced:
▪ O2 uptake in under ventilated areas is reduced
Low V/Q Ratio – Reduced Ventilation ▪ O2 uptake in relatively overventilated areas can’t
compensate since 99% of O2 is transported bound to
Hb & Hb is already 97.5% saturated.
• Ventilation is lower compared to perfusion (i.e. physiological
2. Total blood CO2 content can be normal:
shunting of blood).
▪ Diffusion capacity of CO2 is higher than O2 (due to
• Leads to impaired gas exchange: higher solubility).
o Alveolar PO2 & PCO2 tend to move towards venous ▪ So, CO2 not removed from under ventilated areas can
values (40 & 46mmHg respectively). be removed from over ventilated areas.
o Arterial PO2 is reduced (hypoxemia). PaCO2 is
unchanged (usually) or increased.
• Causes: Any cause of impaired ventilation - decreased Gas Exchange
compliance, increased airway resistance or neural/muscular
problems.
• E.g. Asthma, COPD • Gas exchange is the diffusion of O2 into & CO2 out of the
capillaries, across the alveolocapillary membrane.
• The alveolocapillary membrane consists of the alveolar
High V/Q Ratio – Reduced Perfusion epithelium, endothelium of blood vessels & their fused
basement membranes.
• Gas Exchange is governed by Fick’s Law of Diffusion.
• Perfusion is lower compared to ventilation (i.e. physiological
dead space of alveoli).
• Leads to impaired gas exchange:

1st MBBS Repeat Campaign – 26th Batch
Fick’s Law of Diffusion
• The rate of diffusion of a gas is directly proportional to:
1. Partial Pressure gradient across the alveolocapillary
membrane (I.e. Alveolar PO2 – Capillary PO2)
2. Total Surface Area
3. Diffusion Coefficient of the Gas
▪ DC is directly proportional to the solubility of
the gas
▪ DC is inversely proportional to the molecular
weight of the gas
▪ CO2 is 20 times more soluble than O2, so its
rate of diffusion is higher than O2
• Rate of diffusion is inversely proportional to the thickness of
the alveolocapillary membrane.
Limitations of Gas Exchange
17
• Perfusion Limited Gases:
1. If the rate of diffusion occurs fast enough, Capillary
partial pressure becomes equal to alveolar partial
pressure.
2. Since the partial pressure gradient then becomes zero,
no further diffusion of gas occurs – the gas reaches
equilibrium.
3. Thus, the amount of that gas in blood can’t be
increased by increasing the rate of diffusion but can be
increased by increasing perfusion (blood flow).
4. So, the amount of gas in blood is perfusion limited.
• Diffusion Limited Gases:
1. If the rate of diffusion is too slow, or the gas otherwise
fails to reach equilibrium, the total amount of gas in
blood is limited by the rate of diffusion.
• Limitations of some gases are as follows:
1. N2O – Doesn’t bind with hemoglobin, thus rapidly
equilibrates with blood – Perfusion limited
2. CO2 –
▪ Transported in blood mainly as HCO3-, so it
equilibrates easily.
▪ Since it is more soluble than O2, its diffusion
coefficient and the rate of diffusion is greater
▪ So it is Perfusion limited in both sick & healthy
people (except in severe cases)
3. O2 –
▪ Binds with Hemoglobin, but not rapidly
enough to not reach equilibrium.
▪ Reaches equilibrium in 0.3 sec in healthy
people, so it is perfusion limited in healthy
people.
 18
1st MBBS Repeat Campaign – 26th Batch

▪ Due to its low solubility, in diseases causing
diffusion impairment, O2 may be diffusion
limited in sick people
▪ By giving O2 therapy, alveolar PO2 is increased,
increasing the rate of O2 diffusion & improving
PaO2
4. CO – Binds to hemoglobin with such high affinity that
alveolar PCO doesn’t increase much, so equilibrium
isn’t reached, thus it is Diffusion limited.
• During exercise, diffusion capacity of perfusion limited gases
increases up to 3-fold due to capillary dilatation & recruitment,
which increases perfusion.
• Diseases in which Diffusion Capacity of O2 & CO2 are reduced:
1. Due to a decrease in total surface area – Lung collapse,
consolidation, pulmonary edema, RDS, emphysema
2. Due to an increase in thickness – Pulmonary fibrosis,
Pulmonary edema

Diffusion Capacity Gas Transport

• Volume of gas diffusing across the AC membrane per minute, • Gas diffused into capillary blood must be transported to
per unit partial pressure difference of 1mmHg peripheral tissues. Gases are transported by several methods.
• DLCO – Diffusion Capacity of CO. It is given by the equation: • 99% of O2 in blood is bound to Hemoglobin (1% dissolved in
𝑅𝑎𝑡𝑒 𝑜𝑓 𝐶𝑂 𝑈𝑝𝑡𝑎𝑘𝑒 (𝑉𝐶𝑂 ) plasma). Hb increases O2 carrying capacity 70-fold.
𝐷𝐿𝐶𝑂 =
𝑃𝐴 𝐶𝑂 − 𝑃𝑎 𝐶𝑂 • 94.5% of CO2 in blood undergoes chemical reactions (e.g.
hydrolysis). These reactions increase CO2 carrying capacity 17-
• PaCO is usually zero but it must be considered in smokers.
fold.
Normal DLCO is 25ml/min/mmHg
• O2 delivery to tissues depends on:
• DLCO Measures:
o Amount of Hb
1. Total Alveolar Surface Area
o Affinity of Hb to O2
2. Thickness of Alveoli
o Ventilation, Perfusion, V/Q Matching, Diffusion
3. Capillary Perfusion
4. Hemoglobin Concentration • Each Hb molecule binds 4 O2 molecules (1 per subunit) by a
process called oxygenation (not oxidation), which is an
DLCO Increased DLCO Decreased exothermic (energy releasing) process.
Polycythemia Anemia
Left to Right Intracardiac Shunts Pulmonary Fibrosis
Alveolar Hemorrhage Pulmonary Oedema Cooperative Binding of O2

• Each Hb molecule has 2 α & 2 β subunits, each containing an

Fe2+ molecule to which O2 is bound. Thus, it is a tetramer.
 19
1st MBBS Repeat Campaign – 26th Batch

• In each Hb molecule, 1 α & 1 β subunit are tightly bound by O2 – Hb Dissociation Curve

hydrophobic interactions, thus forming 2 tightly bound pairs of
subunits.
• The 2 ‘αβ dimer’ groups are bound by loose hydrogen & ionic
bonds.
• In the deoxygenated state, there are many hydrogen bonds
between the 2 αβ dimers – This is the tense state.
• When 1 subunit binds to O2, this causes the break down of
hydrogen bonds between the αβ dimers – This is the relaxed
state.
• In the relaxed state, the affinity of the other subunits of the
same Hb molecule to O2 is increased. So, when the first O2
binds, other O2 molecules bind to the same Hb molecule more
easily. This is known as cooperative binding.
• Significance of Cooperative binding:
o In the lung, High PO2 overcomes the low O2 affinity of
deoxyhemoglobin to bind to Hb. Cooperative binding
then helps O2 loading in the lung.
o During transport in blood, Oxyhemoglobin, which now
has a high O2 affinity, effectively transports O2 without
unnecessary loss.
o In tissues, due to low PO2, once the first O2 is removed,
this reduces O2 affinity & facilitates O2 unloading.

• This graph depicts the change in % saturation of Hb with PaO2,

which reflects the O2 affinity of Hb.
• The sigmoid shape of the graph is due to the change from the
tense to relaxed state of Hb, which causes cooperative O2
binding.

1st MBBS Repeat Campaign – 26th Batch
• P50 – This is the arterial partial pressure of O2 at which Hb is
50% saturated. P50 is inversely proportional to the O2 affinity of
Hb. I.e. if P50 increased, O2 affinity is reduced.
Factors Affecting the O2-Hb Dissociation Curve
• A Right shift of the above graph indicates a decrease in O2
affinity (along with an increase in P50). A left shift indicates an
increase in O2 affinity.
• The following factors affect O2 affinity of Hb & the graph:
1. Temperature – Since binding of O2 to Hb is an energy
releasing process, increasing temperature causes a
decrease in O2 affinity of Hb (right shift)
2. pH – An increase in H+ ions (i.e. decrease in pH) causes
increased Hydrogen bonding between the Hb subunits,
stabilizing the tense state, thus decreasing O2 affinity
(right shift)
3. 2,3-BPG – Binding of 2,3 -Bisphosphoglycerate to the β
subunits of Hb stabilizes the tense state, thus
decreasing O2 affinity (right shift). 2,3-BPG is produced
in RBCs by an offshoot of the glycolytic pathway in
response to hypoxia. Its synthesis is inhibited by
acidosis.
Bohr Effect
• This states that Deoxyhemoglobin binds H+ more actively than
Oxyhemoglobin.
• In other words, if the pH is low, it causes formation of more
deoxyhemoglobin, thus decreasing the O2 affinity of Hb.
𝐻𝑏𝑂2 + 𝐻 + ⇌ 𝐻𝐻𝑏 + 𝑂2
20
• Most of the O2 release from Hb at tissues is due to the decrease
in PO2, while 1-2% is due to the Bohr effect.
Changes in O2 Transport During Exercise
• Physiological changes during exercise result in the decrease in
O2 affinity of Hb.
• This facilitates O2 unloading at the tissues, which increases O2
supply to the tissue.
• The following changes take place:
1. Tissue PO2 reduces (due to increased use) while arterial
PO2 remains unchanged (due to increased ventilation).
Thus, partial pressure gradient is increased, which
facilitates O2 dissociation.
2. Body temperature is increased – decreases O2 affinity
3. pH is decreased – Due to CO2 & lactic acid. Decreases O2
affinity.
4. 2,3-BPG is increased, especially in untrained athletes.
CO2 Transport in Blood
• The solubility of CO2 is much higher than O2, so a much larger
proportion can be transported dissolved in blood. 94.5% of Co2
undergoes chemical reactions, which increases the carrying
capacity.
 21
1st MBBS Repeat Campaign – 26th Batch

In Plasma Haldane Effect

1. Dissolved (as CO2)
2. Forms Carbamino compounds with plasma proteins • This states that Deoxyhemoglobin binds with CO2 & forms
3. Undergoes Hydrolysis: Reacts with water to form H+ & carbaminohemoglobin more readily than Oxyhemoglobin.
HCO3- : • Significance:
a. H+ buffered by protein 1. CO2 uptake is facilitated in tissues
b. HCO3- dissolved in plasma 2. CO2 transport capacity is greater in venous blood than
arterial blood
In Red Blood Cells – CO2 Diffuses Across Cell Membrane 3. CO2 release is facilitated at the lungs

1. Undergoes Hydrolysis: Similar to the reaction in plasma

but much more prominent due to the presence of
Carbonic Anhydrase Enzyme:
a. H+ buffered by Hb
b. 30% of HCO3- remains in the RBC. 70% of HCO3- is
exchanged for Cl- in plasma by Anion Exchanger 1
(AE-1). This is called chloride shift.
2. Forms Carbaminohemoglobin (11% of total CO2
transport)
3. Dissolved (as CO2)

Regulation of Respiration
 22
1st MBBS Repeat Campaign – 26th Batch

thoracic α motor neurons innervating the diaphragm &

intercostal muscles, overriding & bypassing autonomic control
Central Controller:
up to certain limits.
1. Pre-Botzinger complex
(Medulla)
2. Pneumotaxic Centre (Pons) Central Controller – Brainstem Respiratory Centre
Afferents Efferents
1. Glossopharyngeal 1. Phrenic Nerve
Nerve
Medullary Components:
2. Intercostal Nerve
2. Vagus Nerve
1. Pre-Botzinger Complex:
o Contains pacemaker cells that initiate & maintain
Effectors rhythmic respiration, & controls respiratory rate.
Sensors (Receptors) o Opioids inhibit the complex. Substance P released in
1. Diaphragm
1. Medullary response to pain stimulates the complex, increasing
Chemoreceptors 2. Intercostal respiratory rate.
Muscles 2. Dorsal & Ventral Groups of Respiratory Neurons
2. Peripheral
Chemoreceptors 3. Accessory o Communicates with the Pre-Botzinger complex, exact
role in respiration unclear.
o Damage doesn’t abolish respiration.
Stimulus Effect
1. Hypoxia 1. Altered Rate of
Pontine Component – Pneumotaxic Centre
2. Respiration
Hypercapnia 2. Altered depth of
• Influences discharge of the medullary controller.
3. Acidosis • Plays a role in switching between inspiration & expiration, so
4. Non- controls Tidal Volume.
• Damage results in slow rate of respiration with increased tidal
Neural Control of Respiration volume.
NOTE: Apneustic center is another respiratory controller located in
• Normally, autonomic, involuntary control is maintained by the the pons, which is involved in some abnormal breathing patterns.
respiratory center in the brainstem.
• Voluntary control is established by the cerebral cortex via
corticospinal tracts sending impulses directly to cervical &
 23
1st MBBS Repeat Campaign – 26th Batch

Stimuli

Chemical
Hypercapnia (Increased PaCO2)
Hypoxia (Decreased PaO2)
Acidosis (Decreased pH)
Non-Chemical
Stretch & Irritation of Lungs
Emotions – Signals from
Hypothalamus & Limbic System
Exercise – Proprioceptors in
Joints, Muscles, Tendons, etc.
Baroreceptors

Chemical Regulation of Respiration – A Negative Feedback Mechanism

• Set Points (Norms): Chemical regulation adjusts ventilation such

that:
o PaCO2: 36-46mmHg
o PaO2: 80-95mmHg
o pH: 7.35-7.45
• If there is an increase in PaCO2, decrease in PaO2, or a decrease
in pH, it stimulates chemoreceptors, which in turn stimulate
the respiratory center.
• If there is an increase in PaO2, decrease in PaCO2 or increase in
pH, it slightly inhibits the respiratory center.
• In healthy people, PaCO2 plays the major role in regulation of
respiration; an increase in PaCO2 stimulates the respiratory
center (Hypercapnic Drive).
• In people with chronic type 2 respiratory failure, the
hypercapnic drive is lost (see below), and PaO2 plays the main
role (Hypoxic Drive).

1st MBBS Repeat Campaign – 26th Batch
Chemoreceptors
Central Medullary Chemoreceptors
• These chemoreceptors are in the medulla, close to the
respiratory center.
• They are highly sensitive to [H+] in the CSF but is not sensitive
to [H+] in blood (i.e. pH) since H+ can’t cross the blood-brain
barrier.
• They are sensitive to PaCO2, since CO2 easily crosses the blood-
brain barrier & dissolves in the CSF:
𝐶𝑂2 + 𝐻2 𝑂 ⇌ 𝐻 + + 𝐻𝐶𝑂3−
Thus, plasma CO2 directly affects [H+] in the CSF, & indirectly
stimulates the respiratory center.
• Up to 70% of the stimulation of the respiratory center due to
CO2 occurs due to stimulation of the central chemoreceptors.
• Central chemoreceptors have zero sensitivity to O2. Since they
also have very low sensitivity to blood pH, Central
chemoreceptors are only stimulated (or inhibited) by changes
in PaCO2.
Peripheral Chemoreceptors
• There are 2 main peripheral chemoreceptors:
1. Carotid Body – afferents travel via the
glossopharyngeal nerve.
2. Aortic Body – Found in the aortic arch, afferents travel
via the vagus nerve.
NOTE: ‘Bodies’ contain the chemoreceptors. Baroreceptors are
found in the Carotid Sinus & Aortic Arch walls.
24
• Both bodies have a special artery supplying them, & have a very
high blood flow for their size.
• Therefore, dissolved O2 (PaO2) is enough for its needs.
Hemoglobin saturation levels by O2 (SaO2 ) doesn’t affect
stimulation (But SaO2 levels are proportional to PaO2 as per the
O2 – Hb dissociation curve).
• The reflex mediated by the peripheral chemoreceptors are
much faster than the central chemoreceptors.
• Peripheral Chemoreceptors are stimulated by:
1. Decreased PaO2 (Only after PaO2<60mmHg)
2. Increased PaCO2 (up to 30% of the response)
3. Decreased blood pH
• Both bodies contain specialized cells; Type 1 & 2 Glomus cells:
o Type 2 glomus cells are supportive in function
o Type 1 glomus cells are sensitive to O2: They contain O2
gated K+ channels; Hypoxia causes closure of these
channels, which cause depolarization, triggering the
release of Dopamine & ATP which stimulate the
afferent nerve endings.
• Stimulation of peripheral chemoreceptors sends afferent
impulses via the relevant nerves to the Nucleus Tractus
Solitarius (NTS) in the medulla, which in turn stimulates the
respiratory center.
Response to Changes in CO2
• Acute changes in CO2 regulates normal ventilation in healthy
people (hypercapnic drive).
• Increase in CO2 stimulates respiration, which in turn increases
CO2 removal (CO2 Washout), which reduces respiration. This is a
negative feedback mechanism.

1st MBBS Repeat Campaign – 26th Batch
Patients with Chronic Hypercapnia (Type 2 Respiratory Failure) are
Desensitized to Changes in PaCO2
• Elevated CO2 (hypercapnia) initially causes respiratory acidosis.
• In chronic cases, this acidosis is compensated by the kidneys,
which reduce HCO3- excretion & increases H+ excretion (renal
compensation).
• This leads to an elevation of blood [HCO3-]. This in turn
increases [HCO3-] in CSF:
𝐶𝑂2 + 𝐻2 𝑂 ⇌ 𝐻 + + 𝐻𝐶𝑂3−
• This buffers H+ in CSF, therefore desensitizing central
chemoreceptors to CO2 levels in blood. I.e. the hypercapnic
drive is lost.
• In these patients, the hypoxic drive is the main mechanism that
drives respiration.
• Excessive O2 therapy may abolish the hypoxic drive & inhibit
respiration, leading to CO2 narcosis & death.
• When giving O2 therapy for these patients, a PaO2 of 60mmHg
(or SaO2 of 90%) is targeted instead of the normal PaO2 target of
97mmHg to keep the hypoxic drive intact.
CO2 Narcosis
• Very high PaCO2 levels can cause depression of the respiratory
system (which further increases PaCO2).
• It may then progress to severe headaches, coma & eventually
death if not treated.
• These effects are due to the negative effects of CO2 on tissue
metabolism.
25
Response to Hypoxia
• Increased discharge of peripheral chemoreceptors begins when
PaO2<1oommHg.
• However, it is not significant until PaO2<60mmHg since:
o Any increase in respiratory rate also increases CO2
washout, reducing the hypercapnic response &
inhibiting the central & peripheral chemoreceptors.
o In the hypoxic state, increased Deoxyhemoglobin binds
with H+ & CO2 decreasing their levels & further
inhibiting peripheral chemoreceptors (Bohr &Haldane
effects).
• Beyond 60mmHg, these effects are overcome & hypoxia
strongly stimulates respiration.
Non-Chemical Control of Respiration
Lung Receptors
• Some receptors send afferent signals via myelinated vagal
fibres:
o Slow-Adapting Stretch Receptors: They are
involved in the Hering-Breuer Inflation reflex where
excess lung expansion due to inspiration is
prevented by signals that inhibit inspiration.
Similarly, the Hering-Breuer Deflation reflex
prevents lung collapse.
o Fast-Adapting Irritant Receptors: They are
stimulated by Histamine, resulting in
bronchoconstriction & hyperpnea.

1st MBBS Repeat Campaign – 26th Batch
• Other Receptors (J-Receptors) send signals via
unmyelinated vagal fibres. They are stimulated by lung
hyperinflation & capsaicin (in spicy foods), & result in
increased mucus secretion & increased respiratory rate.
Other Non-Chemical Stimuli
• Emotions may affect respiration: depression may inhibit the
respiratory center, while anger may stimulate it. These changes
are mediated by the limbic system acting via the hypothalamus.
• Baroreceptors, which normally function to regulate blood
pressure, also stimulate the respiratory center. This can be
seen as compensation to maintain adequate O2 supply to
peripheral tissues (O2 Flux) in hypovolemic conditions.
• Cortical Stimuli, & proprioceptive stimuli can stimulate the
respiratory center. This is the most important stimulus for the
increase in respiration during exercise (Since arterial blood gas
levels pH remain constant during exercise, chemical regulation
doesn’t affect respiration except during very intense exercise)
Effects of Hyperventilation
• Normal autonomic regulation of respiration prevents
hyperventilation, but this can be overridden by voluntary
control of respiratory muscles or strong emotional stimuli.
• Hyperventilation affects several systems
Effect on the Respiratory System
26
• After a period of hyperventilation, there is a period of apnea
(absence of breathing), followed by a period of shallow
breathing, then another period of apnea & so on until normal
breathing is restored.
• This occurs due to fluctuations in PaO2 & PaCO2 levels
Effects on the Cardiovascular System
• Decreased PaCO2 causes Direct vasoconstriction, which
increases Total Peripheral Resistance (TPR) & DBP.
• It also inhibits the Vasomotor center.
• Net result is an increase in cardiac output, while the blood
pressure may remain unchanged or slightly increased.
Effects on the Nervous System
1. Carpopedal Spasms – Trousseau’s & Chvostek’s Signs
o Decreased PaCO2 causes respiratory alkalosis
o Results in dissociation of H+ from plasma proteins
o Free Ca2+ in blood binds to plasma proteins, leading to
hypocalcemia, which increases excitability of nerve &
muscle cell membranes.
o Results in spasms of muscles
2. Light Headedness, Dizziness & Paresthesia (pricking sensation)
o Decreased PaCO2 causes vasoconstriction of cerebral
arterioles
o Results in cerebral ischemia, which causes these
symptoms (paresthesia is due to ischemia of relevant
sensory areas of the brain).
 27
1st MBBS Repeat Campaign – 26th Batch

HYPOXIA Anemic hypoxia

• Hypoxia is oxygen deficiency at the tissue level. • Hypoxia due to insufficient amount of functional hemoglobin to
• Major types of hypoxia: carry oxygen.
1. Hypoxic hypoxia • Partial pressure of oxygen in arterial blood is normal.
2. Anemic hypoxia • PaCO2 normal, PvO2 reduced.
3. Stagnant hypoxia • O2 therapy, will only increase dissolved oxygen, so not efficient
4. Histotoxic hypoxia for this.

Hypoxic hypoxia (Hypoxemia) Carbon Monoxide Poisoning

• Hypoxemia is hypoxia due to inadequate oxygenation of • CO reacts with hemoglobin and form carboxyhemoglobin.
arterial blood. Affinity of Hb for CO is 210 times its affinity for O2.
• Causes: • The dissociation curve is shifted to left, because once CO is
1) Breathing air that leads to low alveolar oxygen bound to one heme subunit, the affinity of other subunits for
E.g.: High altitudes– decreased total barometric pressure O2 increases.
2) Problems with ventilation • Symptoms: Cherry red color to skin, nail beds, lips, tongue.
Air way disorders – obstructive sleep apnea, asthma, • Treatment: Hyperbaric Oxygen (O2 hastens the dissociation of
COPD COHb.
Disorders with compliance – pulmonary fibrosis,
pneumothorax, obesity Stagnant (Ischemic) Hypoxia
3) Problems with gas exchange
Changes in factors affecting diffusion at ACM–surface
• Hypoxia due to inadequate blood flow (slow circulation).
area, thickness
• Causes: Peripheral circulatory failure(shock), Congestive cardiac
E.g.: Pulmonary edema, pulmonary fibrosis
4) Ventilation/perfusion mismatch failure.
E.g.: Atelectasis, Pulmonary embolism • PaO2 normal, PvO2 markedly decreased, PaCO2 normal.
5) Anatomical shunts (venous to arterial)
E.g.: Cyanotic congenital heart disease
6) Pump failure
Fatigue of respiratory muscles

1st MBBS Repeat Campaign – 26th Batch
Histotoxic Hypoxia
• Hypoxia due to inactivation of cytochromic & other enzymes
due to poisoning.
• E.g: cyanide which inhibits tissue oxidative processes). So,
tissues unable to use oxygen.
• PaO2 normal, PvO2 increased, PaCO2 normal.
• Treatment: Methylene blue or nitrites, which form
methemoglobin. And that reacts with cyanide forming
cyanmethemoglobin (nontoxic). Hyperbaric oxygen can also be
given.
Signs of hypoxia
a) Cyanosis
• The bluish discoloration of skin due to presence of more
than 5g/dl of deoxyHb in blood.
• In the presence of hypoxia, tissues extract more oxygen
from Hb to compensate, therefore reduced amount of
oxyHb.
• Amount of reduced Hb depends on,
o Total amount of Hb– cyanosis commonly seen in
polycythemia but not in severe anemia.
o Degree of unsaturation of Hb.
o State of capillary circulation.
• Two types of cyanosis,
1. Central cyanosis– due to diseases of heart and lungs. At
lips, tongue, nail tips, earlobes. Warm to touch.
2. Peripheral cyanosis – due to slowed peripheral
circulation. At earlobes, finger tips. Cold to touch.
28
Note; Methemoglobin (slate gray color) simulates cyanosis. In
carbon monoxide poisoning, no cyanosis. COHb is pink in color.
b) Tachycardia
Reflex response to hypoxia.
c) Tachypnoea
Rapid breathing.
d) Dyspnea
Difficult or laboured breathing in which the subject is conscious of
shortness of breath.
Effects of hypoxia
a) Fulminant hypoxia
Eg : Loss of cabin pressure without supplemental O2.
After exposure to PaO2 less than 20mmHg.
Within 10-20s – unconscious and in 4-5 min – brain death.
b) Acute hypoxia at high altitudes (18-25000ft)
Exposure to PaO2 of 20-40mmHg.
Headache \, slurred speech, anorexia, nausea, vomiting, coma,
death.
c) Chronic hypoxia high altitudes (10-18000ft)
Exposure to PaO2 of 40-60mmHg over extended periods of time.
Cheyne-Stokes breathing (alternating hyperpnoea & apnoea)
 29
1st MBBS Repeat Campaign – 26th Batch

Respiratory Failure • Oxygen delivery devices – Nasal cannula, simple mask,

tracheostomy mask, T-piece, oxygen flow meter.

• Definition – A syndrome in which the respiratory system fails in

one or both of its gas exchange functions: Oxygenation &
Carbon dioxide elimination.

Type 1 Type 2
Arterial oxygen tension (PaO2) < Hypoxemia common in patients
60mmHg breathing room air
Arterial cardbondioxide tension PaCO2 > 50mmHg
(PaCO2) – Normal / low
Failure in lungs Failure in pump
Oxygenation failure Ventialtion failure
Eg : Asthma Eg : Severe asthma
COPD COPD
Pneumonia Myasthenia gravis
Pulmonary fibrosis Poliomyelitis
Pulmonary embolism Obesity-hypoventilation
syndrome

• Acute respiratory failure – if it comes abruptly; pH – acidic

• Chronic respiratory failure – if it comes slowly; pH – low normal

or near normal

Oxygen therapy

• Hypoxemia – when PaO2 < 60mmHg (Normal PaO2 80 –

100mmHg).
 30
1st MBBS Repeat Campaign – 26th Batch

High altitude
Normal (sea level)- Barometric pressure =760 mm Hg
21
O2 = x760 mm Hg
100
=159.6 mm Hg

When passing along respiratory tract.

Gets mixed with H2O and CO2 and is diluted.

Therefore PAO2 100 mm Hg
Physiological shunt.

PAO2 95 mm Hg

When ascending high altitudes,

0-3000 m 3000-4500 m 500-6100 m >6100 m
PaO2 PaO2 60 mmHg ventilation. Loss of consciousness.
Gradual hypoxia therefore hypoxia becomes uneffective
Therefore few in maintaining PAO2
symptoms. Hyperventillation.
Little effect on Profound hypoxia.
respiratory drive. CO2 washed off. (Hypoxic hypoxia)
Therefore hypoxia.
Respiratory alkalosis

• Using 100% breathing O2 above 6100m delay effects of high altitude by maintaining higher PaO2 at high
altitude
• In acclimatized people,delayed effects occur due to hypoxia.

Acute mountain High altitude cerebral oedema High altitude pulmonary oedema
sickness.
• Occurs 11-20 hrs after If capillary leakage of mountain Vasoconstriction occur due to

arrival at altitude. sickness progresses. hypoxia in pulmonary

• Lasts 4- days. capillaries and arteries.

Low O2( <20 mmHg) hypoxia Front brain swelling.

(not all pulmonary arteries
 31
1st MBBS Repeat Campaign – 26th Batch

If cerebral autoregulation doesn’t Ataxia, disorientation, coma. have smooth muscles)

compensate. Therefore pul. pressure in
capillaries
Cerebral vasodialation, Death due to herniation of brain .
Capillary pressure Treatment- Large doses of Patchy oedema due to
Glucocorticoids pulmonary hypertension.
Transudation of fluid into brain Treatment- Nifedipine-reduce
tissue. Pulmonary arterial pressure
• Causes -headaches
Irritability
Insomnia
Breathlessness
Nausea
Vomiting .

• Treatment to all high altitude illnesses;

 Descent to low altitudes
 Diuretic Acetazolamide- Inhibit Carbonic anhydrase.

PaCO2

Formation of CSF.

Acclimatization.
➢ Occurrence of variety of compensatory mechanisms to increase altitude
tolerance.
➢ Hyperventilation at high altitude Rate and depth of respiration.
Therefore respiratory alkalosis shift O2 dissociation curve to left.

But, 2,3 BPG levels of RBC right shift.

Net effect small increase in P50 (O2 affinity )

Slight decrease because otherwise O2 uptake at lungs impaired.

❖ Principles means by acclimatization comes;

1) Increase in pulmonary ventilation. 2) Increase in RBC and Hb concentration.

low PO2 hypoxia Erythropoietin stimulated
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1st MBBS Repeat Campaign – 26th Batch

stimulate arterial chemoreceptors. RBC production -polycythemia

(ventilation )
Haematocrit ( 40-60)
CO2 washing off( PCO2 )
Hb conc (14- 20 g/dl)
pH ( respiratory alkalosis)

therefore blood volume (by 20-30%)

ventilation compensated
inhibited by decrease in
HCO3- conc. 4) Increased vascularity of peripheral tissues.
inhibition fades
- Cardiac output increases about 30% on
immediate ascent.

ventilation due to hypoxic stimulus Later comes to normal when haematocrit

therefore blood O2 transport to tissues,
3)Increased diffusing capacity normal.
- Growth of increased numbers of systemic
Pulmonary lung pulmonary circulatory
capillaries. Arterial pressure
Capillary blood volume
Volume therefore therefore perfusion
Capillary surface alveolar of apices
Area capillary surface area
Permanent inhabitants due to acclimatization
• Barrel shaped chest
• Polycythemia
• Large heart
• [Hb] therefore O2 quantity.
• Venous PO2 very low.

Diving and underwater.

Boyle’s law
1
The compessed volume of a given quantity of gas ∞
𝑝𝑟𝑒𝑠𝑠𝑢𝑟𝑒
∴ increased pressure can collapse the air chambers of a diver’s body.
Effect of high partial pressures of individual gases.
• Nitrogen narcosis.
▪ Molecular N2 comprises 80% of air
▪ At normal barometric pressures, a non reactive gas,but highly lipid soluble.
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1st MBBS Repeat Campaign – 26th Batch

▪ At high barometric pressures, N2 enters blood according to Henry’s law.

( Henry’s law- when temperature is constant, the volume of a gas going into a given liquid is
proportional to the partial pressure of the gas.)

▪ Then N2 escapes blood vessels and dissolves in lipid membranes, especially neuronal
membranes ∴ reduces neuronal excitability becomes anesthetic.
∴N2 narcosis occurs.
▪ The symptoms vary with depth and duration of the diver,
About 120 ft Jovial / carefree demeanor.
120- 200ft Drowsy
200-250 ft loss of strength
>250ft unconsciousness.

• O2 toxcity.
▪ When PO2 in blood > 100mmHg amount of O2 dissolved in blood markedly.
( amount of O2 bound Hb doesn’t increase beyond saturation of Hb)
▪ ∴ the total amount of O2 delivered at the tissues
▪ Acute O2 poisoning occurs seizures followed by coma, nausea ,muscle twitching,
dizziness, disorientation.

• C02 poisoning.
▪ Usually diving gear are designed properly, so that CO2 poisoning doesn’t occur. (
because in depth doesn’t PCO2 in alveoli.)
▪ If an equipment with a large dead space is used ,
-Exhaled CO2 accumulates in the dead space and diver breathes this CO2
- ∴rate and depth of respiration increase.
- If PCO2 in alveoli >50 mmHg respiratory centre becomes depressed

Impaired ventilation- acute repiratory acidosis.

Decompression sickness
• Occurs when diver rapidly ascends, returning to atmosphere from underwater.
• Mechanism –
▪ Gases dissolve in tissues according to - Time spent,depth of dive, type of gas.
▪ The tissues have reached an equilibrium with the high dissolved (N2) pressure.
▪ If diver suddenly ascends, the pressure on te outside becomes 760 mmHg while
pressure inside = pressure of all gases (> 4000mmHg)
∴gases (mainly N2) becomes decompressed.
▪ Gas escapes from tissues forming air bubbles(mainly N2)
▪ These bubbles in,
Blood vessels air embolism ∴occlusion of vessels. Tissue ischemia
Coronary arteries myocardial ischemia
Pulmonary capillaries shortness of
Breath, pulmonary oedema
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1st MBBS Repeat Campaign – 26th Batch

Joints and muscles “ bends”

▪ Treatment Recompression in a pressure chamber.

(lowering the pressure gradually in a pressurized tank0
Hyperbaric O2 therapy.

To prevent N2 narcosis,He is used in very deep dives because

1) He has only 1/5 th the narcotic effects of N2.
2) Only about half as much as volume of He dissolve in body as N2 , and the volume of
that does dissolve, diffuses out rapidly than N2 ∴ lesser problem of decompression
sickness.
3) Low density of He keeps airway resistence

High pressure nervous syndrome.

▪ Many gases when are physiologically inert at atmospheric pressure have anesthetic
effects at increased pressure.
Eg: Xe,Ar, Ne, He
▪ Symptoms - Tremors
Drowsiness
Depression of activity of EEG
Intellectual function not severely affected
Impaired manual dexterity.