Physiology of Human Respiratory

System

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 INTRODUCTION

What is respiration?
Respiration = the series of exchanges that leads to
the uptake of oxygen by the cells, and the release of
carbon dioxide to the lungs.

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 Introduction… cont’d

The term respiration includes three separate but related functions:

1)Ventilation (breathing).
2)Gas exchange, which occurs b/n the air and blood in the lungs and
b/n the blood and other tissues of the body
3)Oxygen utilization by the tissues for energy-liberating

 Ventilation and the exchange of gases b/n the air and blood are
collectively called external respiration.
 Gas exchange b/n the blood and other tissues and oxygen
utilization by the tissues are collectively known as internal
respiration.

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 Stages of Respiration
1. Pulmonary ventilation: gas exchange between the
atmosphere and lungs

2. External respiration -gas exchange between the lungs and

blood (O2 loading and CO2 unloading).

3. Transport of respiratory gases –via movement of blood O2

from the lungs is transported to the cell and tissues.

4. Internal respiration –gas exchange between the capillaries

and the tissues (O2 unloading and CO2 loading).

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Schematic View of Respiration

External Respiration

Internal Respiration

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Physiological classification of the respiratory tract
1. Conducting Zone
Rigid conduits for air
to reach site of gas
exchange
-nose/mouth
-nasal cavity
-pharynx
-larynx
-trachea
-bronchi
-Terminal bronchioles
2. Respiratory
Zone/exchange portion
Site of gas exchange
-respiratory bronchioles
-alveolar ducts 6
Functional Anatomy
 Nasal Cavity
 Nosal-airway
 moistens (raises incoming air to 100% humidity)

 warms air (raises incoming air to 370 c)

 filters inspired air (forms mucociliary escalator)

 resonating chamber for speech via paranasal sinuses that

include:
Frontal sinuses
Sphenoidal sinuses
ethmoidal sinuses
maxillary sinuses
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 Pharynx
 Funnel-shaped tube of skeletal muscle
 Common passageway for:
 Food
 Fluid
 Air
 Located between:
• Nasal cavity and mouth superiorly
• Larynx and esophagus inferiorly
 It breaks into:
• Oesophagus: used for food and fluid passage
• Larynx /voice box (Adam’s apple)

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 Larynx (Voice Box)
 Attaches to the hyoid bone and opens into the laryngopharynx
superiorly and continuous with the trachea inferiorly
 Extends from C3 to C6 and consists of
 Epiglottis, hyoid bone, thyroid cartilage, cricoid cartilage,
vocal cords and glottis
 The three functions of the larynx are:

 To provide a patent airway

 To act as a switching mechanism to route air and food into

the proper channels
 Responsible for voice production 10
 Trachea
 Musculo-cartilagenous tube extending from the larynx into the
mediastinum (10-12 cm long & 2 cm diameter)
 Branches into two bronchi each of which breaks into 23
generations of progressively smaller bronchi, terminal
bronchioles and respiratory bronchioles
 Composed of three layers

 Mucosa – made up of goblet cells and ciliated epithelium

 Submucosa – connective tissue deep to the mucosa

 Adventitia – outermost layer made of C-shaped rings of

hyaline cartilage 11
 Bronchi
 Result of tracheal bifurcation making the 1st to 4th generations

 Air reaching the bronchi is:

 Warmed and cleansed of impurities

 Saturated with water vapor

Bronchioles and Terminal bronchioles

 Are extension of bronchi that makes up the 5th-16th generations

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 Respiratory Zone/Exchanging zone
 Defined by the site of exchanging of respiratory gas

 Includes:
 Respiratory bronchioles with alveoli in their walls, make up
the 17th-20th generations;
 Alveolar ducts, making up the 21st-23rd generations terminate in
alveolar sacs
 Approximately there are 300 million alveoli:

 Account for most of the lungs’ volume

 Provide tremendous surface area for gas exchange

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14
 Respiratory Zone…con’d
 The alveoli
 The functional units of the respiratory system
 Are small out-pouchings or tiny air sacs that are final branching
of the respiratory tree.
 About 300 million alveoli in the lung  surface area for exchange
(60–80 m2, 40x surface area of the body)
 Each alveolus is 1 cell layer thick  rate of diffusion
 Do not contain muscle because muscle fibers would block rapid
gas exchange. However, it contains elastin and collagen fibers
that create elastic recoil when lung tissue is stretched
 Contain open pores that:
 Connect adjacent alveoli
 Allow air pressure throughout the lung to be equalized
 Respiratory Zone

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 Respiratory Membrane

 Respiratory Membrane is composed of:

 Alveolar and capillary walls

 Alveolar walls:

 Are a single layer of type I epithelial cells

 Permit gas exchange by simple diffusion

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Respiratory Membrane

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 Lungs
 On a volume basis they are among
the largest organs of the body next
to that of skin.
 Lung subdivided as:
• Right lung is separated into
three lobes- superior, middle,
inferior and accounts for 55% of
pulmonary function.
• Left lung is separated into upper
and lower lobes and accounts for
45% of the pulmonary function.

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 Physical Properties of the Lungs
 Compliance:
 Distensibility (stretchability):
 Ease with which the lungs can expand.
 100 x more distensible than a balloon.
 Compliance is reduced by factors that produce
resistance to distension.
 Elasticity:
 Tendency to return to initial size after distension.
 High content of elastin proteins.
 Very elastic and resist distension.
 Recoil ability
 General Functions of the Respiratory System
 Primary Functions
 Extra-cellular respiration:
- Conduction of air to and from the terminal air spaces.
 Intracellular respiration: utilization of O2 & production of CO2
 Secondary Functions
Deglutition and modification of inspired air,
Defense of body against noxious stimuli like inhaled particles,
Olfaction, phonation, conduction of air.
Acid-base balance,
Regulation of various humoural concentrations(ACE)

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Respiratory Muscles and their motor innervations

i. Diaphragm: innervated by Phrenic nerves arising from C3-C5

ii.Intercostals: innervated by intercostal nerves from thoracic
segments
iii. Tracheo-broncheal tree: innervated by:
- Parasympathetic NS→bronchial constriction and secretions
- Sympathetic NS→bronchial dilatation and decreased
bronchial secretions.

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 Mechanism of Ventilation/ Breathing

 Terminology

• Inspiration = the movement of air into the respiratory tracts.

• Expiration = movement of air out of the respiratory tracts.

• Respiratory cycle = is one inspiration followed by an

expiration.
• Ventilation = Mechanical process that moves air in
(Inspiration)
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and out (Expiration) of the lungs.
 Structure involved during ventilation

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 Mechanics (work) of Inspiration and Expiration/
Mechanism of Ventilation

Movement of thorax  Movement of lungs through linkages of

thin film of lymph between the lungs and chest wall  sliding of
lungs over the chest wall.

NB: The lungs are separated from the respiratory muscles by the
pleural space.

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• INSPIRATION enlargement of chest cavity volume
of thorax-ve PplLung expansion

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 Inspiration…
 Inspiration( quit normal breathing)

– Intra alveolar pressure falls from 0 to -1 mmH2O

– Intrapleural pressure falls further to -7.5 mmH2O

– Transpulmonary pressure raises to +6 mmH2O

 Net= 0.5(500ml) of air gushs to the lungs in 2-3 seconds.

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EXPIRATION: Reduction in chest cavity↓volume of

thorax↓-ve Ppl ↓lung vol.

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 During Expiration
Passive at rest Active during exercise

Elastic recoil of: Surface tension Nerve impulses

effect of: ↓
Contraction of :
Stretched tissues Fluid lining • expiratory muscles (internal
in thorax, lungs alveoli and
and abdominal respiratory intercostals)
muscles bronchioles •ant. abdominal muscles
↓ ↓ including pelvic floor muscles
30% of TV 70%TV ↓
Upward movement of diaph.
 Expiration …

 Expiration:(quit normal breathing)

– Intra alveolar pressure raise from -1 to +1 mmH2O

– Intrapleural pressure raise from -7.5 to -4 mmH2O

– Transpulmonary pressure falls to +5 mmH2O

 Net= 500ml of air is expehaled from the lungs.

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 Types of Breathing - Abdominal and Thoracic
 Movement of chest wall Thoracic breathing.
 Movement of diaphragm displacement of abdominal viscera
and abdominal wall Abdominal breathing
 At rest, abdominal breathing accounts for 70% and thoracic
breathing for 30% of the ventilation.
 During vital capacity measurement, thoracic breathing accounts
for 70% of the air moved.
 In pregnancy and ascites, breathing is mainly thoracic.
 During deep breathing both abdominal and thoracic breathing are
equal in magnitude.
 The work of breathing is higher in thoracic than in abdominal
breathing.
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 Air Flow

 Air flow dynamics develop due to driving pressure in the

airways.
 Air flow occurs whenever there is a pressure gradient.
 Bulk flow of air, like blood flow, is directed from areas of
higher pressure to areas of lower pressure
 Inspiration: PB-PA=+ve pressure as applied in resuscitation.
 Expiration: PA-PB = +ve pressure
 Air flow in the respiratory tract obeys the same rule as blood
flow:
Flow  P /R where, P =change in P
R= resistance
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 What Elements Oppose Air Flow?

Forces Opposing Air flow

1. Resistance (R): flow term pertaining to airways
 Opposition to motion

2. Elastance (E): volume term pertaining to connective tissue

Ability of tissue to return to its original shape (recoil or
retract) after deformed by some external force.
Reciprocal of compliance.
E= strain /stretch = Δp/V

3.Inertance(I): acceleration term pertaining to lung mass

 A dynamic rate of change of flow.
These forces are overcome by trans-pulmonic pressure.
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 Airway Resistance
Airway resistance(R) determines the rate of gas flow (F) for a
given pressure gradient from the alveolus to the mouth (ΔP).
According to Ohm’s law, F  P /R

There are 3 factors that affect resistance to air flow:

1.Airway radius (r)- main component of airway resistance
•The upper airway offers significant resistance, and then
declines rapidly from the 4th through the 10th generation.
2. Lung volume
•At low lung volume, the cross-sectional area is reduced and
airway resistance increases.
• For example, patients with pulmonary fibrosis have low lung
compliance and low resting lung volume; high airway
resistance
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3. Turbulent gas flow

 Increases airway resistance.

 Disorganization of the gas stream requires more pressure to
drive flow and effectively increases resistance.
 Bronchoconstriction reduces the airway diameter and
increases the velocity of flow.
High velocity causes turbulent flow, which generates a
wheezing
sound (e.g., in asthma).
NB: Airway resistance increases during forced expiration because
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intrapleural pressure becomes positive and the airways are
 Maximum resistance is in
medium sized bronchi then
drops as cross sectional area
increases.
NB: Air flow resistance through
nose and naso-pharynx = 2/3
of total resistance.

• Resistance of airways distal to

12th generation of branching
=10% of total resistance.

• Largest fraction of Raw and

greatest pressure gradient
occur between trachea and
bronchi.
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 Airway Resistance….

 As airway resistance(Raw) rises, breathing movements become

more strenuous.
 Severely constricted or obstructed bronchioles:

• Can prevent life-sustaining ventilation

• Can occur during acute asthma attacks which stops ventilation

 Epinephrine released via the sympathetic nervous system dilates

bronchioles and reduces air resistance

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 Compliance of the lungs
• Describes elastic (stretch) properties of lungs and thorax.
• Is change in lung volume per unit change in distending trans-
mural pressure across the lung (C=ΔV/ΔP).
• Determined in a subject by a stepwise instilling of 50-100ml of air
at a time and measurement of p at the end of each step; then air
removed also in steps.
• Depends not only stretchability of lung tissue but also on the
surface tension of the air-water interfaces within the alveoli.
• Lungs inflated with saline have no fluid-air interface to produce
any surface tension effect ,i.e. have a much larger compliance and
a smaller hysteresis (are easier to distend) than air-filled lungs
(Fig. below).
• Hysterisis: is a phenomenon of differing volume/pressure curves
on inflation and deflation.
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 Compliance of the lungs…cont’d

 There are two types of compliance: static and dynamic.

 Static compliance is the measurement of lung stretchability
when the lungs are not moving.
 Normal mean value of static compliance=0.30 L/cmH2O.
 Static compliance is always a higher value than dynamic.
 Dynamic compliance is the measurement of the lungs when in
motion, at the end of inspiration and expiration.
 Dynamic compliance is measured by dividing the tidal volume,
by the difference between the pressure of the lungs at full
inspiration and full expiration.

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 Compliance of the lungs…cont’d

Factors that reduce compliance

Ca2+, Tb
Asbestosis, Silicosis
Pulmonary fibrosis, Pulmonary oedema, Kyphosis
Chronic poor ventilation

Factors that increase compliance

Emphysema
Aging of the lung structure

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 Surface Tension
 Force exerted by fluid in alveoli to resist distension.
 Lungs secrete and absorb fluid, leaving a very thin film of fluid
 This film of fluid causes surface tension.
 Water molecules at the surface are attracted to other water
molecules by attractive forces.
 Force is directed inward, raising pressure in alveoli.

 air out of inner alveolar surfaces.

 This leads to a collapse tendency of the lungs.
Law of Laplace

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 Alveoli could collapse to smallest size (contracted) if there is no
counter-acting force.
 Fortunately, there are two forces to counteract this.

1. Surfactant which markedly reduce the cohesive forces.

2. Pressure in alveoli (P) = 2T/r, when one surface is involved in

liquid-lined spherical alveolus, and P=4T/r when both surfaces
are involved.
• This pressure keeps alveoli normally distended.

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NB: if the surface tension were the same;

1. Large alveoli (large radii) have low pressure and are easy to
keep open.

2. Small alveoli (small radii) have high pressure and are difficult
to keep open.
• In the absence of a surfactant, the small alveoli have a tendency
to collapse and empty into large alveoli.

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Deep inspirationExpansion of alveolisurface area of fluid
dispersion of surfactant↓surfactant effect surface tension
Expiration  recoil of alveoli to smaller size↓fluid surface
area condensed surfactantsurfactant activity ↓surface
tension
• Surface tension during inspiration  prevention of alveolar
over-distension and rupture.
• ↓Surface tension during expiration  prevention of lung collapse.

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 Surfactant
 Surfactant is a complex mixture of several phospholipids,
proteins, and ions
 Important components are the phospholipid
dipalmitoylphosphatidylcholine, surfactant apoproteins, and
calcium ions.
 Surfactant is a surface active agent in water, which means that it
greatly reduces the surface tension of water.
 Reduces attractive forces of hydrogen bonding by becoming
interspersed between water molecules.
 Lung collapse is resisted by three forces:
1) Actions of surfactant
i. Surfactant is:
• hydrophobic at one end and hydrophilic at the other;
• interspersed in b/n liquid molecules lining the alveoli and
air in the alveoli thus making a repulsive force low surface
tension compliance (distensibility) of lung work of
breathing.
ii. Surfactant promotes stability of alveoli, i.e. prevents alveolar
collapse by balancing pressure between small and large alveoli;
iii. Surfactant keeps the alveoli dry by preventing transudation of
fluid through the reduction of surface forces/ reduce the
tendency to develop pulmonary edema

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2) Distending Pressure of alveoli
 Collapse tendency is overcome by distending pressure
generated by alveolar surface forces.
 Distending pressure is predicted from La Place’s law: P= 2T/r
for one surface, P=4T/r for two surfaces, where T=tension in
wall, r = radius of alveoli.
 Increased radius of alveoli surface tension collapse
tendency of lung because distending pressure falls with
increased radius.

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 3)Mechanical interdependence of
alveoli
 An alveolus tending to collapse
pulls away from its neighboring
alveoli thus increasing stress on
their walls.
 The neighbors pull its wall out and
prevent its collapse.
 This is how pulling forces of the
alveoli keep them all open.

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 Respiratory Volume and Capacity

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 Respiratory Volume and Capacity

The process of recording the volume of air moving into and out

of the lungs, with different phases of respiration is a called

spirometry.
The equipment used in the process is called spirometer.
There are about four lung volume and four lung capacity.

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 Respiratory Volume and Capacity….
Lung volumes
 Tidal volume (TV) – air that moves into and out of the lungs
with each breath (approximately 500 ml)
 Inspiratory reserve volume (IRV) – air that can be inspired
forcefully beyond the tidal volume (3000 ml)
 Expiratory reserve volume (ERV)- volume maximum
expiration (1200ml)
 Residual volume (RV) – air left in the lungs after maximal
expiration (1300 ml)
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 Respiratory Volume and Capacity….
Lung Capacities

 Vital Capacity (VC) – the total amount of exchangeable air

(TV + IRV + ERV)
 Inspiratory Capacity (IC) - the sum of TV and IRV

 Functional Residual Capacity (FRC) -the sum of RV& ERV

 Total Lung Capacity (TLC) – sum of all lung volumes

(approximately 6000 ml in males)

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 Respiratory Volume and Capacity…..

 RV, FRC and TLC can not measure directly with simple spirometer
Techniques used to estimate FRC, TLC etc.
• Closed circuit He dilution technique
• Open circuit N2 wash out technique
Factors affecting lung volumes and capacities
• age, sex, posture, body type, physical training

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Restrictive Disease:
– Makes it more difficult to get air in to the lungs.

– They “restrict” inspiration.

– Decreased VC, TLC, RV, FRC

– Includes:

• Fibrosis

• Sarcoidosis

• Muscular diseases

• Chest wall deformities

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 Obstructive Disease
– Make it more difficult to get air out of the lungs.

– Decrease VC; Increased TLC, RV, and FRC

– Includes:

• Emphysema

• Chronic bronchitis

• Asthma

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 61
Fig. Dry Spirometry (Vitalography)
I.

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 Fg.11b.
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II.
 Limitations of Spirometry

 Provides useful diagnostic and screening information but the

patterns of tracing showing restrictive or obstructive conditions
are not disease-specific, i.e. record does not specify the disease as
asthma, emphysema, etc.
 Additional information such as physical exam, CXR, etc are
needed to make a diagnosis.
 Cannot be done with 100% accuracy because of limited
cooperation of study subject or patient.

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 Dead Space
 The part of the respiratory system where gas exchange does not
take place is called the dead space.
1. Anatomic dead space
• Conduction air ways are fixed dead space
• Its volume is 150 ml
2. Alveolar dead space
• Unperfused but ventilated alveoli
• Pulmonary embolism increases
3. Physiologic dead space
• Sum of anatomic and alveolar dead space
• In diseases this becomes large resulting in hypercapnea and
hypoxemia
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July 15, 2024 65

 Quantifying Dead Space

 Composition of alveolar gas is constant in breathing cycles

 PECO2 is lower than PACO2 because, high PECO2 mixes with low CO2
of the dead space
 As dead space becomes larger PECO2 become smaller
 Hence the difference between PECO2 and PACO2 is a function of dead
space (Bohr equation )
 Alveolar ventilation

 Is the room air delivered to the respiratory zone per minute.

 It is calculated the tidal volume(VT) minus the dead space

volume(VD) multiplied by respiratory rate(f).

 If a person inhales 500 mL of air and 150 mL of it is dead air,

then 350 mL of air ventilates the alveoli
 The alveolar ventilation rate is a major factor affecting the
concentrations of oxygen and carbon dioxide in the alveoli.

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 Gas Exchange and Transport

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 Gas Exchange and Transport
 Air is a mixture of gases, each of which contributes a share,
called its partial pressure, to the total atmospheric pressure.

 The partial pressure of nitrogen is PN2, for example; Nitrogen

constitutes about 78.6% of the atmosphere, thus at1atm of
pressure, PN2 = 78.6% x 760mmHg = 597 mmHg.

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 Dalton’s law
 States that the total pressure of a gas mixture is the sum of the
partial pressures of the individual gases.

 That is, PN2+ PO2+PH2O +PCO2=597.0 +159.0 +3.7 + 0.3= 760.0

mmHg.
 These partial pressures are important because they determine
the rate of diffusion of a gas and therefore strongly affect the
rate of gas exchange between the blood and alveolar air.

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 The greater the PO2 in the alveolar air, the more O2 the blood
picks up. And, since the blood arriving at an alveolus has a
higher PCO2 than air, the blood releases CO2 into the air.

 At the alveolus, the blood is said to unload CO2 and load O2.

 Each gas in a mixture behaves independently; the diffusion of

one gas does not influence the diffusion of another.

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 Alveolar Gas Exchange
 Alveolar gas exchange is the process of O2 loading and CO2
unloading in the lungs through simple diffusion
 Since both processes depend on erythrocytes (RBCs), their
efficiency depends on how long an RBC spends in an alveolar
capillary compared to how long it takes for O2 and CO2 to reach
equilibrium concentrations in the capillary blood.

 A RBC passes through an alveolar capillary in about 0.75 second

at rest and 0.3 second during vigorous exercise, when the blood
is flowing faster. But it takes only 0.25 second for the gases to
equilibrate, so even at the fastest blood flow, a RBC spends
enough time in a capillary to load as much O2 and unload as
much CO2 .
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 The following factors especially affect the efficiency of
alveolar gas exchange:
• Concentration gradients of the gases.
• Solubility of the gases.
• Square root of molecular wt of the gas(mw)
• Membrane thickness (0.5 nm)
• Membrane area (70 m2).
• Absolute temperature of fluid
• Permeability of membrane
• Fluid viscosity in lung ()
• Contact or transit time of gas
• Ventilation-perfusion coupling.
• Exercise or change in metabolic rate
• Opening of more capillaries3-4 folds due to dilatation
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of existing capillaries.
 The PO2 is about 104 mmHg in the alveolar air and 40 mmHg in
the blood arriving at an alveolus.
 Oxygen therefore diffuses from the air into the blood, where it
reaches a PO2 of 104 mmHg.

 Before the blood leaves the lung, however, this drops to about 95
mmHg because blood in the pulmonary veins receives some
oxygen-poor blood from the bronchial veins by way of
anastomoses.
 The PCO2 is about 46 mmHg in the blood arriving at the alveolus
and 40 mmHg in the alveolar air.
 Carbon dioxide therefore diffuses from the blood to the alveoli.

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July 15, 2024 75
 According to Fick’s law, the rate of transfer of a gas through a
sheet of tissue is directly proportional to the tissue area, the partial
pressure difference between the two sides, the fluid temperature,
solubility coefficient of the gas , and inversely proportional to
fluid viscosity, thickness of the tissue and square root of
molecular wt. of the gas DG=ΔPTα A/L mw.

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Solubility of the gases.

 Gases differ in their ability to dissolve in water.

 CO2 is about 20 times as soluble as O2, and oxygen is about

twice as soluble as N2.

 Even though the conc. gradient of O2 is much greater than that

of CO2 across the respiratory membrane, equal amounts of the

two gases are exchanged because CO2 is so much more

soluble and diffuses more rapidly.

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 Gas Transport
 It is the process of carrying gases from the alveoli to the
systemic tissues and vice versa.

1) Transport of O2

 The conc. of O2 in arterial blood is about 20 mL/dL.

Mode of Transport

i. Solution (1.5%)

ii. chemical combination with Hb (98.5%)

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 Transport of O2 …..

i. Transport of O2 in dissolved form :

 Henry’s Law of solubility states that the amount of gas that
dissolves in a liquid is directly proportional to:
a) partial pressure of the gas,
b) solubility of the gas.
 For each mm Hg of PO2 there is 0.003 ml O2 / 100 ml of blood
(0.003 vol %).
 Thus, normal arterial blood with a PO2 of 100 mm Hg contains

0.31 ml O2 /100 ml (0.31 vol %).

 Dissolved O2 transport accounts for only about 1.5% of the O2
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transported which is insufficient for tissue need.
 Transport of O2 …..
ii. Chemical combination with Hb

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 Transport of O2 …..
 Each heme group can bind 1 O2 to the ferrous ion at its center;
thus, one hemoglobin molecule can carry up to 4 O2

 If O2 is bound to hemoglobin, the compound is called

oxyhemoglobin (HbO2), whereas hemoglobin with no oxygen
bound to it is deoxyhemoglobin (HHb).

 When hemoglobin is 100% saturated, every molecule of it carries 4

O2; if it is 75% saturated, there is an average of 3 O2 per
hemoglobin molecule; if it is 50% saturated, there is an average of
2 O2 per hemoglobin; and so forth.

 The poisonous effect of CO is from its competition for the O2

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binding site.
 Transport of O2 …..

Amount of O2 combining with 1gm of Hb

- Adult =1.306 ml
- Foetus = 1.312 ml
At PO2 95mmHg in adult:

-dissolved O2= 0.31ml/dl of blood,

-chemically bound O2=19.6 ml/dl of blood

100 ml of arterial blood carrying 20ml of O2 has Hb saturated

with 97-98% of O2.

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 Oxygen dissociation (Delivery) Curve
 O2 forms easily reversible combination with Hb to give
oxyhaemoglobin: O2 +Hb  HbO2

July 15, 2024 83

July 15, 2024 84
 Oxygen dissociation (Delivery) Curve…

 The amount of O2 carried by Hb increases rapidly as a result of

progressively increasing affinity until a PO2 of about 50 mmHg

is reached as shown by the pattern of combination of HbO2-PO2

curve (Fig. below).
 Hb is said to be fully saturated when all four hemes of its
molecule are bound to oxygen and partially saturated when only
one to three of its hemes are bound to oxygen.

NB: There are about 250 million Hb molecules in each RBC and
15 g/dl of blood.
July 15, 2024 85
 Oxygen dissociation (Delivery) Curve…

July 15, 2024 86

 Oxygen dissociation (Delivery) Curve…

 Foetal Hb(Hb F) has greater affinity for O2 than adult Hb(HbA).

 Two of its protein globin chains are gamma chains instead of
beta
chains, 2,3-DPG cannot shift the dissociation curve to the right.
Functionally, Hb F differs from HbA in that it is able to bind
oxygen with greater affinity than the adult form, giving the
developing fetus better access to oxygen from the mother's blood
stream.
 HbF is 20-50% more saturated with O2 than HbA at low PO2
July 15, 2024 87
levels
July 15, 2024 88
 Factors affecting O2 dissociation

Factors Right shift of Left shift of

curve curve
PH +/- - +

Temperature +/- + -

PCO2 +/- + -

2, 3-DPG +/- + -
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July 15, 2024 91
NB:
 CO2 does not compete with O2 because CO2 and O2 bind to
different sites on the hemoglobin molecule.
 Hb can therefore transport both O2 and CO2 simultaneously.

 Where as, CO interferes with the O2 transport by combining with

Hb to form carboxyhemoglobin (COHb).
CO has about 240 times the affinity of O2 for Hb.

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July 15, 2024 93
 Some clinical correlates
1. Hypoxia: induced when
a. PaO2 is decreased
b. Cardiac output is not optimal
c. Tissue uptake and utilization of O2 is impaired
Types of hypoxia:
a. Hypoxic hypoxia: low PO2
b. Hypoemic or anaemic hypoxia: low Hb
c. Stagnant (ischaemic) hypoxia: stagnant blood flow
d. Histotoxic hypoxia: failure of cell to utilize O2
 Cyanosis:
 A bluish discoloration of the skin, lips, nails, etc. due to
excessive arterial deoxy-haemoglobin (>50g/L).
94
 A sign of hypoxia with normal or moderately reduced Hb
2. Use of 100% oxygen
• Indicated for a limited
period of time in:
 CO poisoning
 RDS
 Mediastinal emphysema
 Myocardial infarction
 Reduced CBF and
dizziness
 Convulsions and coma,
etc.
July 15, 2024
3. Hyperoxia and O2 toxicity
• Use of 100% O2 for a prolonged
period of time →
 Irritation of respiratory passages
 Coughing
 Airway hemorrhage
 Nasal congestion
 sub-sternal distress
 O2 toxicity occurs when inspired
O2 is >165 mmHg
 O2 toxicity depends on the level
(300mmHg) and duration of
hyperoxia.
95
 Transport of CO2
 The total CO2 content of arterial blood is about 48 mL/dL of
blood.
 Mixed venous blood contains about 52 mL/dL of blood.

 Carbon dioxide is transported mainly in three forms:

as bicarbonate

as carbamino compounds and

as dissolved gas.

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 Transport of CO2 ….
1. About 90% of the CO2 is hydrated (reacts with water) to form
H2CO3, which then dissociates into HCO3- and H+ inside
RBC.
• The reaction of CO2 and H2O occurs slowly in the blood
plasma but much faster in the RBCs (carbonic anhydrase).
CA
CO2 + H2O  H2CO3  HCO3- + H+

• HCO3- is delivered into plasma via the Cl-/HCO3-

exchange (known as the “chloride shift”).

2. About 5% binds to the amino groups of plasma proteins

and Hb within RBC to form carbamino compounds.
July 15, 2024 97
 Transport of CO2 ….
3. The remaining 5% of the CO2 is carried in the blood as dissolved

gas.

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 Some clinical correlates
1. Hypocapnia : PCO2=15mmHg → apnoea
PO2=120-140mmHg
2. Hypercapnia: PCO2>46mmHg→respiratory acidosis, confusion,
decreased sensory activity, comma and death
3. Acid-base disturbance :: acidemia, alkalemia
4. Effects of CO2 on the body:
• Narcotic effect (Unconsciousness)
• ↓Excitability of neurones
• ↓intracellular pH
 BF in brain

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 Regulation of Ventilation
 The chief function of the lung is to exchange O2 and CO2 b/n

blood and gas and thus maintain normal levels of PO2 and

PCO2 in the arterial blood.

 In spite of widely differing demands for O2 uptake and CO2

output made by the body, the arterial PO2 and PCO2 are
normally kept within close limits.
 This remarkable regulation of gas exchange is made possible
because the level of ventilation is so carefully controlled.
July 15, 2024 102
Control of ventilation consists of the following
structural components:
i. Sensors (receptors) - peripheral and central

ii. Sensory (afferent) nerves

iii. Control centers.

iv. Motor (efferent) nerves

v. Effectors–lungs, respiratory muscles

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July 15, 2024 104
 Basic respiratory centers
 Medulla and Pons : produce and control the respiratory
rhythm
 Automatic (involuntary) breathing center

 Higher respiratory centers:

 cerebral cortex Voluntary breathing center

 hypothalamus & limbic system

 Spinal cord: motor neurons

July 15, 2024 105

1. Sensors that gather information and feed it to the

2. Central controller in the brain, which coordinates the

information and, in turn, sends impulses to the

3.Effectors (respiratory muscles), which cause ventilation.

• Increased activity of the effectors generally ultimately
decreases the sensory input to the brain, for example, by
decreasing the arterial PCO2.

• This is an example of negative feedback.

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 Chemoreceptors
i. Peripheral Chemoreceptors
ii. Central Chemoreceptors

i. Peripheral chemoreceptors: are found mainly in aortic and

carotid bodies.
 Detect changes in :
• PO2
• PCO2: 20-35%
• H+ (pH)- peripheral chemoreceptor in carotid body
 Factors increasing activity of peripheral chemoreceptors:↓PO2,
↓pH, ↓Carotid BF, ↑PCO2, ↑Blood temp.
 Factors decreasing activity of peripheral chemoreceptors
include:↑PO2, ↑pH, ↑Carotid BF, ↓PCO2, ↓Blood temp. 107
 Chemoreceptors…..

ii. Central Chemoreceptors

 Located near the ventral surface of the medulla

 Sensitive to the PCO2 but not PO2 of blood

 Respond to the change in pH of the ECF/CSF when CO2

diffuses out of cerebral capillaries

Factors increasing activity:

• ↑ arterial or CSF H+ emanating from PCO2.
• CO2 and not H+ can cross the blood brain barrier, i.e.
change of arterial pH due to CO2.
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 Control of ventilation ………..

 Inspiration and expiration are produced by the contraction and

relaxation of skeletal muscles in response to activity in
somatic motor neurons in the spinal cord.
 The activity of these motor neurons is controlled, in turn, by
descending tracts from neurons in the respiratory control
centers in the medulla oblongata and from neurons in the
cerebral cortex.

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 Voluntary Control of ventilation
 The cerebral cortex is responsible for coordinating
breathing with voluntary activities.
 Commands from the cerebral cortex can temporarily
override automatic brainstem centers
 originates in the motor cortex of frontal lobe of cerebrum
 send impulses down corticospinal tracts to respiratory
neurons in spinal cord, bypassing brainstem.

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 Voluntary Control of ventilation

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 Involuntary Control of ventilation

 Neurones located in the pons and medulla control the

periodic nature of involuntary respiration (inspiration
and expiration).
 Receptors feed into the brain stem through sensory cranial
nerves.
 The brain stem (medullary centres) consisting of a series
of interconnected neurons (ventral respiratory group
(VRG) and dorsal respiratory group (DRG), and the pons
have two components (apneustic centre (lower Pons) and
pneumotaxic centre (upper Pons)
 The VRG and DRG initiate and maintain spontaneous
expiration and inspiration patterns respectively.

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 INSPIRATION is initiated in the medulla (DRG) and is
enhanced by the apneustic centre (lower Pons).

→ excitation of pneumotaxic centre (upper Pons) + stimulation

of stretch receptors from the chest and thoracic cage) (inflation
reflex).
 This leads to increased frequency of vagal afferent
impulses→inhibition of inspiratory centre by pneumotaxic
centre → excitation of expiratory centre (VRG)
→EXPIRATION, which, if prolonged, is counteracted by
deflation reflex.
July 15, 2024 113
limits duration of inspiration

114
 Ventilator response to CO2

 In normal PO2 the ventilation increases by about 2 to 3L/min

for each 1 mmHg rise in PCO2.

 Lowering the PO2 produces two effects:

 ventilation for a given PCO2 is higher, and the

 slope of the line becomes steeper.
 There is considerable variation between subjects

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  Each curve of total
ventilation
against alveolar PCO2 is for a
different alveolar PO2.

 The slope of the line is

slightly less at the higher PO2.

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 Ventilator response to hypoxia (PO2)

 If the alveolar PCO2 is kept at about 36 mm Hg, stimulation of

ventilation will start when alveolar PO2 reduced to the vicinity

of 50 mm Hg. (Fig.below)
 When the PCO2 is increased, a reduction in PO2 below 100
mmHg causes some stimulation of ventilation, unlike the
situation in which the PCO2 is normal.
 Thus, the combined effects of both stimuli exceed the sum of
each stimulus given separately; this is referred to as
interaction b/n the high CO2 and low O2 stimuli.
July 15, 2024 117
 Fig. Hypoxic response
curves.

Note that when the PCO2 is

35.8 mm Hg, almost no
increase in ventilation
occurs until the PO2 is
reduced to about 50 mm
Hg.

July 15, 2024 118

 Role of respiratory system in acid base regulation

 Lungs help to regulate pH through carbonic acid

bicarbonate buffer system

 Changing respiratory rates changes PCO2

 Respiratory compensation is a change in the respiratory rate

to stabilize the pH of the ECF.
 Respiratory compensation is activated within minutes.

July 15, 2024 119

 1. Chemoreceptors in carotid and aortic sinuses sense changes in
pH of blood; receptors on ventrolateral surfaces of the medulla
oblongata sense changes in pH of the CSF.

2. Receptors are stimulated by a fall in pH (rise in PCO2) and

inhibited by a rise in pH (fall in PCO2).

3. Stimulation increases respiration rate ⇒ more CO2 expired;

PCO2 returns to normal pH.

4. When PCO2 falls, respiration rate decreases and PCO2 rises 

pH.
July 15, 2024 120
 Respiratory acidosis (↓pH, ↑PCO2)
 Respiratory acidosis occurs when the respiratory system is
unable to eliminate CO2 produced from cellular metabolism

 An increase in CO2 increases H+ ion concentration and the

body’s pH starts falling below 7.40

 The increase in PCO2 stimulates chemoreceptors to increase

respiratory rate.
 When ventilation is increased above the normal rate, excessive
amounts of CO2 are excreted in expired air.
July 15, 2024 121
 In this situation CO2 is washed out of the body leading to a
hypocapnia, the pH rises.
 A rise in pH is again sensed by central chemoreceptors in the
medulla and CSF???.

 Both CO2 and H+ concentration reduction resulting in a

decrease in ventilationPco2 pH.

July 15, 2024 122

 Causes of respiratory acidosis
 Caused by hypercapnia due to hypoventilation
 Any condition that impairs gas exchange or lung ventilation
(chronic bronchitis, cystic fibrosis, emphysema, pulmonary
oedema)
 Rapid shallow breathing, hypoventilation
 Narcotic or barbiturate overdose or injury to brain stem
 Airway obstruction
 Chest or head injury
 Effects: muscle weakness, fatigue, drowsiness and coma
July 15, 2024 123
 Compensation:

July 15, 2024 124

 Respiratory alkalosis (↑pH, ↓PCO2)
• Cause: Hyperventilation, Leads to eliminating excessive amounts
of CO2.

• This reduction of PCO2 below the range of 4.5-5.6 kPa (30—35

mmHg) causes a reduction in H+ generation.
• The decreasing H+ concentration raises the blood pH above the
normal range of 7.45
• Any condition that causes hyperventilation can cause a
respiratory alkalosis.

July 15, 2024 125

Causes:
 Direct cause is always hyperventilation (e.g. too much
mechanical ventilation, pulmonary lesions)
 Brain tumor or injury

 Acute anxiety

 Asthma

Effects: Muscle pain, twitching , loss of appetite, headache,

irritability, nausea and vomiting

July 15, 2024 126

 Compensation:

July 15, 2024 127

 The end!

July 15, 2024 128