RESPIRATORY PHYSIOLOGY

(LECTURE NOTE)

A.H. UMAR
 Course objectives
• At the end of the course, students should be able to
– Describe structure and functions of the respiratory system
– List the passages through which air passes from the exterior to
the alveoli.
– List the major muscles involved in respiration, and state the role
of each.
– Explain the mechanism of breathing
– Explain pulmonary blood flow and circulation
– Describe pulmonary ventilation and lung compliance, and role
of surfactants
– State and explain lung volumes and capacities and the
pulmonary function test
– Describe composition of inspired air, expired air and alveolar air,
and physiologic and anatomic dead space
– Explain the transport of respiratory gases
– Describe control of respiration and respiratory changes in
various conditions (i.e. exercise, high altitude and deep sea)
 INTRODUCTION
• Respiration is process of exchange of gases between the living organism and
external environment through breathing.
• The goal of respiration is to provide oxygen to the tissues and to remove
carbon dioxide.
• It involve the production of energy, typically with the intake of oxygen and the
release of carbon dioxide from the oxidation of complex organic substances
• Respiration may be external (exchange of respiratory gases between lungs and
blood/breathing) or internal (utilization of oxygen for energy production).
• The respiratory system provides for gas exchange—intake of O2 and
elimination of CO2
• Other functions of the respiratory system include
– regulating blood pH,
– contains receptors for the sense of smell,
– Filters inspired air,
– Defense against infection. In the alveolar cavity, there are large phagocytic cells
called the pulmonary alveolar macrophages (PAMs).
– Regulate body temperature by removing water and heat in exhaled air
– Secrete angiotensin converting enzyme
– Secrete heparin from mast cells
– Synthesize hormones, e.g. prostaglandins , acetylcholine, serotonin
– produces sounds, and
– Serves as blood reservoir.
 PHYSIOLOGIC ANATOMY
• Respiratory system is composed of the nose, pharynx,
larynx, trachea, bronchi, bronchioles and lungs.
• Structurally, the respiratory system consists of:
– The upper respiratory system: the nose, nasal cavity, pharynx,
and associated structures and
– The lower respiratory system: the larynx, trachea, bronchi and
lungs.
• Functionally, the nasal cavity, pharynx, larynx, trachea,
bronchi, bronchioles, and terminal bronchioles constitute
the conducting zone, a series of interconnecting cavities
and tubes which function to filter, warm, and moisten air
and conduct it into the lungs.
• The respiratory zone is part of the respiratory system
where gas exchange occurs. These include the respiratory
bronchioles, alveolar ducts, alveolar sacs and alveoli. They
are the main sites of gas exchange between air and blood.
 THE LUNGS
• The lungs are paired cone shaped organs that are
separated by the mediastinum
• Each lung is enclosed and protected by a double-
layered serous membrane called the pleural membrane
• The outer parietal pleura lines the wall of the thoracic
cavity, while the inner visceral pleura covers the lungs
themselves
• The parietal and visceral pleurae are separated by
pleural cavity containing pleural fluid, a lubricating fluid
secreted by the membranes.
• The pleural fluid reduces friction between the
membranes, allowing them to slide easily over one
another during breathing and also produce surface
tension.
• The lung is divided by fissures into lobes, and each lobe
receive its own lobar bronchi
• The right lung is divided by the oblique and horizontal
fissures into superior, middle and inferior lobes
• While the left lung is divided by the oblique fissure into
superior and inferior lobes only, due to the cardiac
notch, which makes the left lung about 10% smaller
than the right
• The mediastinal (medial) surface of each lung contains
the hilum, a region through which bronchi, pulmonary
blood vessels, lymphatic vessels, and nerves enter/exit
the lungs
• Within the lung, the lobar bronchi give rise to 10
segmental bronchi
• The segment of lung tissue that each segmental
bronchus supplies is called a bronchopulmonary
segment
• Each bronchopulmonary segment of the lungs has
many small compartments called lobules; each lobule
is wrapped in elastic connective tissue and contains a
lymphatic vessel, an arteriole, a venule, and a branch
from a terminal bronchiole.
• The trachea give rise to left and right main bronchi
• The right main bronchus is more vertical, shorter, and
wider than the left. As a result, an aspirated object is
more likely to enter and lodge in the right main
bronchus than the left.
• Terminal bronchioles subdivide into respiratory
bronchioles, which in-turn divide into several alveolar
ducts (lined by a simple squamous epithelium) that
lead into the alveoli
• As the respiratory bronchioles penetrate more deeply
into the lungs, the epithelial lining changes from simple
cuboidal to simple squamous.
• The structural and functional unit of lungs is called
the respiratory unit. Exchange of gases occur only
through the respiratory unit
• The respiratory unit is made of the respiratory
bronchioles, alveolar ducts, alveolar sacs and the
alveoli.
 Alveolus
• The alveolus is a pouch like structure with a
diameter of about 0.2 to 0.5 mm, lined by
epithelial cells (pneumocytes).
• There are 2 types of alveolar pneumocytes; type I
and type II
• Type I alveolar cells are the squamous epithelial
cells that form about 95% of the total number of
cells. They form the site of gaseous exchange
between the alveolus and blood.
• Type II alveolar cells are cuboidal in nature and
form about 5% of alveolar cells. These cells are
also called granular pneumocytes and they
secrete alveolar fluid and surfactant.
 Surfactant
• Surfactant is a surface active agent in water. It greatly
reduces the surface tension of water.
• Surfactant is a complex mixture of several phospholipids,
proteins, and ions (mostly calcium).
• The most important components are the phospholipid
(dipalmitoylphosphatidylcholine), surfactant apoproteins,
and calcium ions.
• The phospholipid is responsible for reducing the surface
tension.
• It lowers the surface tension of alveolar fluid, which
reduces the tendency of alveoli to collapse and thus
maintains their patency
• It is secreted by type II alveolar cells (type II pneumocytes),
which contain microvilli on their alveolar surface and
constitute about 10 per cent of the alveoli.
Functions of surfactant

• Surfactant reduces the surface tension in the

alveoli of lungs and prevents collapsing
tendency
• of lungs.
• It plays an important role in the inflation of
lungs after birth.
• It play a role in defense within the lungs
against infection and inflammation.
• Deficiency of surfactant causes respiratory
distress syndrome
 Factors that influence formation of the lung
surfactants
• The formation of lung surfactant is stimulated
by:
– thyroid hormones and glucocorticoids, surfactant
proteins (SP-B, SP-C) which are produced by
degradation of lung surfactant. Another surfactant
protein (SP-A) regulates the uptake of (SP-C) by
type II pneumocytes.
• Formation of surfactant is inhibited by:
– insulin, smoking, long term inhalation of pure
oxygen, and cessation of the pulmonary circulation
for a long time (as in open heart surgery when the
patient is put on pump oxygenator).
Respiratory distress syndrome (RDS)
• Respiratory distress syndrome is a breathing disorder
of premature newborns in which the alveoli do not
remain open due to a lack of surfactant.
• The more premature the newborn, the greater the
chance that RDS will develop.
• RDS is more common in infants whose mothers have
diabetes and in males
• Symptoms include labored and irregular breathing,
flaring of the nostrils during inhalation, grunting
during exhalation, and cyanosis (blue skin colour).
• It can be managed by delivering oxygen to the baby
PULMONARY BLOOD FLOW AND CIRCULATION
• From the right ventricle of the heart, deoxygeneted
blood is carried by the pulmonary artery to the lungs
for oxygenation.
• Oxygenated blood return to the left atrium via the
pulmonary vein
• The lung tissue is supplied with oxygen and nutrients
thru the bronchial artery, a branch of descending
thoracic aorta.
• Venous drainage is by bronchial vein.
• Right bronchial vein drain into azygos vein, while the
left bronchial veins drain into acessory hemiazygos or
left superior intercostal veins.
• Some deoxygenated blood from bronchial circulation
empties into pulmonary veins and pass to the left
atrium, forming a physiologic shunt.
• Blood flow to pulmonary circulation = cardiac output (5L/min)
• Pulmonary blood vessels are more distensible than systemic blood
vessels, thus, the blood pressure is less in pulmonary blood vessels.
• The pulmonary vascular system is a low pressure bed.
– Pulmonary Arterial Pressure:
• Systolic pressure : 25 mm Hg
• Diastolic pressure : 10 mm Hg
• Mean arterial pressure : 15 mm Hg.

• Pulmonary capillary pressure is about 7 mm Hg. This pressure is

sufficient for exchange of gases between alveoli and blood.
• Factors that regulate pulmonary blood flow include:
– Cardiac output
– Vascular resistance
– Nervous factors
– Chemical factors
– Gravity and hydrostatic pressure.
 PULMONARY VENTILATION
• Air flows between the atmosphere and the alveoli of
the lungs because of alternating pressure differences
created by contraction and relaxation of respiratory
muscles.
• The rate of airflow and the amount of effort needed for
breathing are also influenced by alveolar surface
tension, compliance of the lungs, and airway resistance
• Respiration occurs in two phases; inspiration and
expiration.
• Air moves into the lungs when the air pressure inside
the lungs is less than the air pressure in the
atmosphere.
• Air moves out of the lungs when the air pressure inside
the lungs is greater than the air pressure in the
atmosphere.
• Pulmonary ventilation is defined as the volume of air
that moves in and out of respiratory tract in a given
unit of time during quiet breathing.
• It is also called minute ventilation or respiratory minute
volume (RMV).
• Pulmonary ventilation is a cyclic process, by which
fresh air enters the lungs and an equal volume of air
leaves the lungs.
• Normal value of pulmonary ventilation is 6,000 mL (6
L)/minute. It is the product of tidal volume (TV) and
respiratory rate (RR).

– Tidal volume × Respiratory rate

– 500 mL × 12 breaths/minute
=6,000 mL/minute.
• Breathing is the act of inspiration and
expiration, which occurs in a regular cyclical
manner.
• During rest a breathing cycle consists of 3
phases: inspiration, expiration, followed by a
short expiratory pause.
• Breathing occurs regularly at a rate of 12-15
breaths per minute in adults
• Eupnea = Easy breathing during rest.
• Tachypnea = Increase in frequency without
increase in depth of breathing.
• Hyperpnea = Increase in frequency and depth
of breathing.
Muscles of breathing
• Primary inspiratory muscles are the external
intercostal muscles, supplied by intercostal
nerves (T1 to T11), and the diaphragm, which is
supplied by phrenic nerve (C3 to C5).
• Accessory inspiratory muscles;
sternocleidomastoid, scalene, serratus anterior,
levator scapulae and pectoral muscles.
• Primary expiratory muscles are the internal
intercostal muscles, which are innervated by
intercostal nerves.
• Accessory expiratory muscles; serratus superior,
inferior, rectus abdominis.
Respiratory pressures
• Two types of pressures are exerted in the thoracic
cavity and lungs during process of respiration:
• Intra-pleural pressure or intra-thoracic pressure:
pressure existing in pleural cavity, between the visceral
and parietal layers of pleura. It is exerted by the suction
of the fluid that lines the pleural cavity. It is always
negative to (less than) atmospheric pressure.
• The normal pleural pressure at rest is about –5 cmH2O.
This is the amount of pressure required to hold the
lungs open to their resting level.
• During normal inspiration, expansion of the chest cage
pulls outward on the lungs with greater force and
creates more negative pressure, to an average of about
–7.5 cmH2O.
• Intra-alveolar pressure or intra-pulmonary pressure:
pressure of air existing in the lung alveoli.
• At rest (between breaths), it is equal to atmospheric
pressure. It becomes negative during inspiration and
positive during expiration
• During normal inspiration, alveolar pressure decreases to
about –1 cmH2O.
• This slight negative pressure is enough to pull 0.5 liter of air
into the lungs during normal quiet inspiration.
• During expiration, the alveolar pressure rises to about +1
cmH2O, and this forces the 0.5 liter of inspired air out of the
lungs.
• The difference between the alveolar pressure and the
pleural pressure gives the transpulmonary pressure. It is
the pressure difference between that in the alveoli and that
on the outer surfaces of the lungs. It is a measure of the
elastic forces in the lungs that tend to collapse the lungs
(recoil pressure).
Mechanism of breathing
• Boyle’s law: pressure α 1/volume
• When volume ↓se, pressure ↑se
• At rest, the intra-pulmonary (intra-alveolar) pressure is equal to
atmospheric pressure.
• During inspiration, contraction of external intercostal muscles move
the ribs upward and outward, causing an increase in the
anteroposterior and lateral diameters of the thorax
• The dome-shaped diaphragm also contract and and move
downward, towards the abdomen, causing increase in vertical
diameter of the thorax
• The above two phenomenon cause increase in volume of the
thoracic cavity.
• The intra-pulmonary pressure now decreases, becoming lower than
atmospheric pressure.
• Air moves into the lungs
• NB: Contraction of the external intercostals is responsible for about
25% of the air that enters the lungs during normal quiet breathing.
• Normal expiration during quiet breathing is a passive
process because no muscular contractions are involved.
• Expiration results from elastic recoil of the lungs and chest
wall, both of which have a natural tendency to recoil after
they have been stretched.
• As the diaphragm relaxes, its dome moves superiorly owing
to its elasticity.
• As the external intercostals relax, the ribs are depressed.
• These movements decrease the vertical, lateral, and
anteroposterior diameters of the thoracic cavity, which
decreases lung volume.
• In turn, the alveolar pressure increases above atmospheric
pressure
• Air then flows from the area of higher pressure in the
alveoli to the area of lower pressure in the atmosphere
The respiratory membrane
• Exchange of O2 and CO2 between the air in the lungs and the blood takes
place by diffusion across the alveolar and capillary walls, which together
form the respiratory membrane
• It is formed by the alveolar membrane and capillary membrane, and
separates air in the alveoli from the blood in capillary.
The respiratory membrane consists
of four layers:
•A layer of type I and type II
alveolar cells and associated
alveolar macrophages that
constitutes the alveolar wall
•An epithelial basement
membrane underlying the
alveolar wall
•A capillary basement
membrane that is often fused
to the epithelial basement
membrane
•The capillary endothelium
 LUNG COMPLIANCE
• Compliance is defined as change in volume per unit change
in pressure
• It is the ability of the lungs and thorax to expand, i.e. it is
the expansibility of lungs and thorax.
• Compliance is a measure of stiffness of lungs. The stiffer
the lungs, the less is the compliance
• Compliance refers to how much effort is required to stretch
the lungs and chest wall.
• High compliance means that the lungs and chest wall
expand easily; low compliance means that they resist
expansion.
• Lung compliance is related to elasticity and surface tension.
• The lungs normally have high compliance and expand easily
because elastic fibers in lung tissue are easily stretched and
surfactant in alveolar fluid reduces surface tension.
Pressure-volume curve
• Factors that increase lung compliance include old age,
Emphysema (due to destruction of elastic fibers in alveolar
walls).
• Factors that decrease lung compliance include:
– Lung compliance decreases in conditions such as tuberculosis,
pulmonary edema, deficiency of surfactant (respiratory distress
syndrome), paralysis of the intercostal muscles,
– Deformities of thorax like kyphosis and scoliosis
– Fibrotic pleurisy (inflammation of pleura resulting in fibrosis)
– Paralysis of respiratory muscles
– Pleural effusion (accumulation of large amount of fluid in pleural
cavity)
– Pneumothorax (presence of air), hydrothorax (presence of
water), hemothorax (blood in thorax) and pyothorax
(accumulation of pus in pleural cavity).
– Lung compliance is lower in lungs with smaller size(e.g. a patient
with one lung has approximately half the compliance of a
normal person)
– It is lower during inspiration than during expiration.
Work of breathing
• Work of breathing is the work done by respiratory muscles during
breathing to overcome the resistance in thorax and respiratory tract
• During normal quiet breathing, all respiratory muscle contraction occurs
during inspiration, while expiration is almost entirely a passive process
caused by elastic recoil of the lungs and chest cage.
• Thus, under resting conditions, the respiratory muscles perform “work” to
cause inspiration but not to cause expiration.
• During the work of breathing, the energy is utilized to overcome three
types of resistance:
– Elastic resistance of lungs and thorax (compliance)
– Nonelastic viscous resistance (tissue resistance).
– Airway resistance

• Thus, the work of inspiration can be divided into three fractions:

– (1) that required to expand the lungs against the lung and chest elastic forces,
called compliance work or elastic work;
– (2) that required to overcome the viscosity of the lung and chest wall
structures, called tissue resistance work; and
– (3) that required to overcome airway resistance to movement of air into the
lungs, called airway resistance work.
Work of breathing
 LUNG VOLUMES AND CAPACITIES AND LUNG
FUNCTION TEST
• Tidal volume: Amount of air breathed in or out of the
lungs during normal quiet breathing. About 500mL
• Inspiratory reserve volume: Amount of air that can be
inspired forcefully after normal inspiration. About
3300mL
• Expiratory reserve volume: Amount of air that can be
expired forcefully after normal expiration. About 1000mL
• Residual volume: Amount of air that remains in lungs
even after forced expiration. About 1200mL. It helps to
maintain the contour of the lungs and to aerate the
blood in between breathing.
• Vital capacity: TV + IRV + ERV
• Inspiratory capacity: TV + IRV
• Functional residual capacity: ERV + RV
• Total lung capacity: TV + IRV + ERV + RV
• The lung volumes and capacities are measured
using a spirometer
• Graphical record of lung volumes using
spirometer is a Spirogram
• Spirometer cannot be used to measure
residual volume, instead, RV is measured by
helium dilution technique, nitrogen washout
method or plethysmography.
Timed Vital Capacity/Force Expiratory Volume (FEV)
• FEV is the volume of air, which can be expired
forcefully in a given unit of time (after a deep
inspiration).
• It is a dynamic lung volume.
– FEV1 = Volume of air expired forcefully in 1 second
– FEV2 = Volume of air expired forcefully in 2 seconds
– FEV3 = Volume of air expired forcefully in 3 seconds
• Normal FEV1 is about 80% of the vital capacity.
• FEV1 is a test for the airway resistance.
• In obstructive lung diseases (e.g. bronchial asthma)
vital capacity is reduced and FEV1 is markedly
reduced.
• FEV is highly reduced in obstructive diseases (like
asthma and emphysema), and is slightly reduced in
some restrictive respiratory diseases like fibrosis of
lungs
Peak Expiratory Flow Rate (PEFR)
• Is the maximum rate at which the air can be expired
after a deep inspiration
• It is normally about 400 litres/min.
• It is the measure of the power of muscles of
expiration and the respiratory airway resistance.
• It is measured by using Wright peak flow meter
• It is reduced in conditions that weakens the
expiratory muscles or increase the airway resistance.
• PEFR is useful for assessing respiratory diseases
• PEFR is reduced in all type of respiratory disease.
However, reduction is more significant in the
obstructive diseases than in the restrictive diseases.
• Thus, in restrictive diseases, the PEFR is 200
L/minute and in obstructive diseases, it is only 100
L/minute
 ABNORMALITIES OF BREATHING
• Apnea: Apnea is defined as the temporary arrest
of breathing (absence of breathing).
• Apnea can be produced voluntarily, which is
called breath holding or voluntary apnea
• Apnea occurs voluntarily, after hyperventilation
or during swallowing (deglutition apnea)
• Clinically, apnea is classified into:
• Obstructive Apnea
• Occurs because of airway obstruction mainly due
to excess tissue growth like tonsils and adenoids.
• Common obstructive apnea occurs in sleep (Sleep
apnea)
• Sleep apnea is the temporary stoppage of breathing
that occurs repeatedly during sleep. It commonly
affects overweight people.
• Major cause for sleep apnea is obstruction of upper
respiratory tract by excess tissue growth in airway, like
enlarged tonsils and large tongue.
• It is characterized by loud snoring.
• Central Apnea
• Central apnea occurs due to brain disorders, especially
when the respiratory centers are affected.
• It is seen in premature babies and is characterized by a
short pause in between breathing.
Hyperventilation
• Hyperventilation means increased pulmonary ventilation due to
forced breathing.
• In hyperventilation, both rate and force of breathing are increased
and a large amount of air moves in and out of lungs.
• Thus, pulmonary ventilation is increased to a great extent.
• Very often, hyperventilation leads to dizziness, discomfort and
chest pain
• Hyperventilation may be produced voluntarily or during exercise
Hypoventilation
• Hypoventilation is the decrease in pulmonary ventilation caused by
decrease in rate or force of breathing.
• The amount of air moving in and out of lungs is reduced.
• „Hypoventilation occurs when respiratory centers are suppressed or
by administration of some drugs.
• It occurs during partial paralysis of respiratory muscles
Dyspnea
• Dyspnea means difficulty in breathing.
• Physiologically, dyspnea can occur during
severe muscular exercise
• It can also occur due to respiratory disorder
(e.g. pneumonia, pulmonary oedema), cardiac
disorder (left ventricular failure, mitral
stenosis), or metabolic disorder (like diabetic
acidosis, uremia).
 Cheyne-Stokes breathing
• Cheyne-Stokes breathing is the abnormal or
uneven respiratory rhythm characterized by
rhythmic hyperpnea and apnea.
• It is the most common type of periodic breathing
and is marked by alternate patterns of
hyperpneic period followed by apneic period.
• Cheyne-Stokes breathing occur during deep
sleep, in high altitude, after prolonged voluntary
hyperventilation, in newborn babies and after
severe muscular exercise
• Pathologically, it occur in increased intracranial
pressure, cardiac failure, uremia, narcotics
poisoning, and in premature infants.
Emphysema

• Emphysema is a disorder characterized by destruction

of the walls of the alveoli, producing abnormally large
air spaces that remain filled with air during exhalation.
• It causes less surface area for gas exchange, and O2
diffusion across the damaged respiratory membrane is
reduced.
• Blood O2 level is decreased, and any mild exercise that
raises the O2 requirements of the cells leaves the
patient breathless.
• It is generally caused by a long-term irritation; cigarette
smoke, air pollution, and occupational exposure to
industrial dust.
 ALVEOLAR VENTILATION
• The ultimate importance of pulmonary ventilation is to
continually renew the air in the gas exchange areas of
the lungs, where air is in proximity to the pulmonary
blood.
• These areas include the alveoli, alveolar sacs, alveolar
ducts, and respiratory bronchioles.
• The rate at which new air reaches these gas exchange
areas is called alveolar ventilation.
• Alveolar ventilation is thus the amount of air utilized
for gaseous exchange every minute
• Dead space air is excluded in alveolar ventilation

• Alveolar ventilation = (Tidal volume – Dead space) x RR

– (500 – 150) mL × 12/minute
= 4,200 mL (4.2 L)/minute.
Dead space
• Dead space is the part of the respiratory tract, where gaseous exchange
does not take place.
• Air present in the dead space is called dead space air
• Dead space can be anatomical dead space or physiological dead space
• Anatomical dead space includes nose, pharynx, trachea, bronchi and
branches of bronchi up to terminal bronchioles.
• These structures serve only as the passage for air movement, as gaseous
exchange does not take place in these structures
• Physiological dead space includes anatomical dead space and also air in
the alveoli which do not receive adequate blood flow, and in the alveoli
which are non-functioning.
• In some respiratory diseases, alveoli do not function because of
dysfunction or destruction of alveolar membrane.
• Dead space air is measured using Nitrogen washout method
• Normally, the anatomic and physiologic dead spaces are nearly equal
because all alveoli are functional in the normal lung
• Normal volume of dead space air is 150 mL
COMPOSITION OF INSPIRED AIR, ALVEOLAR AIR
AND EXPIRED AIR
• Oxygen, carbon (IV) oxide, nitrogen and water vapour are the major
respiratory gases
• They are present in inspired air, alveolar air, expired air, arterial blood,
body tissues and venous blood
• The gases exert partial pressures which are proportional to their individual
concentrations (Dalton’s law of partial pressure)
• According to Dalton’s law of partial pressure; each gas in a mixture of
gases exerts its own pressure as if no other gases were present.
• If there is a mixture of gases which do not react chemically together, each
gas exerts a partial pressure equal to the pressure it would exert if it alone
filled the container at the same temperature and pressure
• The pressure of a specific gas in a mixture is called its partial pressure
• The total pressure of the mixture is calculated simply by adding all of the
partial pressures.
• For e.g., atmospheric air is a mixture of gases—nitrogen (N2), oxygen (O2),
argon (Ar), carbon dioxide (CO2), variable amounts of water vapor (H2O),
plus other gases present in small quantities.
• Atmospheric pressure (760mmHg) is the sum of the pressures of all of
these gases
• Pressure exerted by each component in the mixture can be determined by multiplying
the percentage of the gas in the mixture by the total pressure of the mixture.
• E.g. O2 = 20.9%, PP of O2 = 0.209 X 760, = 158.8 mmHg
• PP of CO2 in inspired air is low (0.3mmHg).
• As the air gets to the alveolus, PP of CO2 in
alveolar air rises to 40mmHg because a lot of CO2
diffuses from the pulmonary capillary into the
alveolus
• PP of O2 in inspired air is high (159mmHg), but it
is reduced in the alveolus (104mmHg) because
O2 diffuse from alveolus into pulmonary capillary
• PP of O2 in expired air is higher than in alveolar
air because of mixture with dead space air during
expiration
• Reverse occurs for CO2
Ventilation-perfusion ratio
• Ventilation-perfusion ratio is the ratio of alveolar
ventilation and the amount of blood that perfuse
the alveoli.
• Ventilation-perfusion ratio = VA/Q.
– VA = alveolar ventilation (4,200mL/minute)
– Q = pulmonary blood flow (5000mL/minute).
• Normal value = 0.84
• Ventilation-perfusion ratio signifies the gaseous
exchange. It is affected by change in alveolar
ventilation or in blood flow.
– Ventilation without perfusion = dead space
– Perfusion without ventilation = shunt
• Variations in ventilation-perfusion ratio:
– Change in ventilation
– Change in blood flow
– Sitting/standing position: In sitting position, there is
reduction in blood flow in the upper part of the lungs
(zone 1) than in the lower part (zone 3). Therefore, in
zone 1 of lungs ventilation-perfusion ratio increases
three times. At the same time, in zone 3 of the lungs,
because of increased blood flow ventilation-perfusion
ratio decreases
– In chronic obstructive pulmonary diseases (COPD, e.g.
asthma), ventilation is affected because of obstruction
and destruction of alveolar membrane. So,
ventilation-perfusion ratio reduces greatly
 GAS LAWS IN RELATION TO RESPIRATION
• Air is a mixture of gases and air flow is similar to blood flow, as the driving
force for air flow is a pressure gradient and it is opposed by resistance (Air
flow = ∆ P/∆ R)
• Gas laws relevant to respiration include:
• Boyle’s law: states that the pressure of a given mass of gas is inversely
proportional to its volume provided the temperature remain constant
– P α 1/V, P1V1 = P2V2
– This law is important in the mechanism of breathing
• Dalton’s law of partial pressure: states that in a mixture of gases, each gas
exerts a partial pressure equal to the pressure it would exert if it were
alone at the same temperature and pressure
• Dalton’s law is important in explaining PP of gases in inspired air, alveolar
air, expired air, arterial blood, venous blood and tissue fluid
– Pressure exerted by each component in the mixture can be
determined by multiplying the percentage of the gas in the mixture
by the total pressure of the mixture.
– E.g. in atmospheric air, O2 = 20.9%, PP of O2 = 0.209 X 760, = 158.8
mmHg
• Graham’s law of diffusion: states that under equal conditions of
temperature and pressure, gases diffuse at rates inversely
proportional to the square roots of their molecular masses.

– R = rate of diffusion
– M = molecular mass
• Fick’s law of diffusion: Fick's laws of diffusion were derived
by Adolf Fick in 1855. It states that the rate of diffusion of a
substance through a membrane is directly proportional to the area
of the membrane (A), solubility of the substance in the membrane
(S), and the concentration gradient of the substance across the
membrane and inversely proportional to the thickness of the
membrane (t), and the square root of the molar mass of the
substance (M).
• Fick’s law help to explain exchange of gases across
membrane
• According to Fick’s law, amount of a substance crossing a
given area is directly proportional to the area available for
diffusion, concentration gradient and a constant known as
diffusion coefficient
• Henry's law: It was formulated by William Henry in 1803
and states that at equilibrium, the amount of a gas
dissolved in a liquid at a constant temperature is directly
proportional to the partial pressure of the gas in the gas
phase.
• Thus, if the pressure of the gas is doubled, the amount of
gas in solution will be doubled
• This law help in explaining the transfer of gases from
alveolar sac into the pulmonary blood, and then into the
red blood cell
 TRANSPORT OF RESPIRATORY GASES
• Exchange of respiratory gases takes place at the lungs and tissue
levels by bulk flow diffusion.
• At the lungs, O2 diffuse from alveoli into the blood, and CO2 from
blood to alveoli
• At tissue level, the opposite takes place.
• Oxygen transport consist of four steps:
– Movt from air into alveoli (inspiration)
– Diffusion from alveoli into blood
– Transport to tissue and
– Diffusion from systemic capillary into tissue
• Diffusing capacity for oxygen is 21 mL/minute/1 mmHg. Diffusing
capacity for carbon dioxide is 400 mL/minute/1 mmHg. Thus, the
diffusing capacity for carbon dioxide is about 20 times more than
that of oxygen
• Diffusing capacity is defined as the volume of gas that diffuses
through the respiratory membrane each minute for a pressure
gradient of 1 mmHg.
 Factors Affecting Diffusing Capacity
• Diffusion capacity is directly proportional to:
– Pressure gradient
– Solubility of gas
– Surface area of respiratory membrane
• It is inversely proportional to:
– Molecular mass of gas
– Thickness of respiratory membrane
• Gases diffuse along their pressure gradient
• Partial pressure of oxygen in the atmospheric air is 159 mm Hg and in the
alveoli, it is 104 mm Hg. Because of the pressure gradient of 55 mm Hg,
oxygen easily enters from atmospheric air into the alveoli
• Partial pressure of oxygen in the pulmonary capillary is 40 mm Hg and in
the alveoli, it is 104 mm Hg. Pressure gradient of 64 mm Hg facilitates the
diffusion of oxygen from alveoli into the blood
• Partial pressure of carbon dioxide in alveoli is 40 mm Hg whereas in the
blood it is 46 mm Hg. Pressure gradient of 6 mm Hg is responsible for the
diffusion of carbon dioxide from blood into the alveoli
• In atmospheric air, partial pressure of carbon dioxide is only about 0.3 mm
Hg whereas, in the alveoli, it is 40 mm Hg. So, carbon dioxide passes to
atmosphere from alveoli easily due to very high pressure gradient
• At the tissue level, Oxygen enters the cells of tissues from blood and
carbon dioxide is expelled from cells into the blood also along pressure
gradient.
• Partial pressure of oxygen in the arterial end of systemic capillary is only
95 mm Hg.
• Average oxygen tension in the tissues is 40 mmHg.
• Thus, a pressure gradient of about 55 mm Hg exists between capillary
blood and the tissues so that oxygen can easily diffuse into the tissues
• Partial pressure of carbon dioxide is high in the cells and is about 46 mm
Hg. Partial pressure of carbon dioxide in arterial blood is 40 mm Hg.
Pressure gradient of 6 mm Hg is responsible for the diffusion of carbon
dioxide from tissues to the blood
• During strenuous exercise or other conditions that greatly increase
pulmonary blood flow and alveolar
• ventilation, the diffusing capacity for oxygen increases to about 65
ml/min/mm Hg,
• This increase is caused by opening up of many previously dormant
pulmonary capillaries or extra dilation of already open capillaries, thereby
increasing the surface area of the blood into which the oxygen can diffuse,
and also due to a increase in ventilation-perfusion ratio
 Respiratory exchange ratio and respiratory
quotient
• Respiratory exchange ratio (R) is the ratio between the net output
of carbon dioxide from tissues to simultaneous net uptake of
oxygen by the tissues (R = CO2 output/O2 intake)
• Respiratory quotient is the molar ratio of carbon dioxide production
to oxygen consumption. It is used to determine the utilization of
different foodstuffs
• Value of R depends upon the type of food substance that is
metabolized.
• When a balanced diet is utilized, R is about 0.825.
• However, when a person utilizes only carbohydrates for
metabolism, R is 1.0. During carbohydrate metabolism, the amount
of carbon dioxide produced in the tissue is equal to the amount of
oxygen consumed.
• If only fat is used for metabolism, the R is 0.7 because when fat is
utilized, oxygen reacts with fats and a large portion of oxygen
combines with hydrogen ions to form water instead of carbon
dioxide. So, the carbon dioxide output is less than the oxygen
consumed, and the R is less.
• If only protein is utilized, R is 0.803.
• For about 1 hour after meals, the respiratory quotient
is 1.0. It is because usually, immediately after taking
meals, only the carbohydrates are utilized by the
tissues.
• During the metabolism of carbohydrates, one molecule
of carbon dioxide is produced for every molecule of
oxygen consumed by the tissues, thus, the respiratory
quotient is equal to respiratory exchange ratio.
• After utilization of all the carbohydrates available, body
starts utilizing fats. Now the respiratory quotient
becomes 0.7. When the proteins are metabolized, it
becomes 0.8.
• respiratory quotient increases during exercise
Transport of oxygen
• Once oxygen has diffused from the alveoli into the pulmonary
blood, it is transported to the peripheral tissues
• Oxygen is transported in two forms in the blood, i.e. dissolved in
plasma (only 0.3mL/100mL) or in combination with haemoglobin
(about 97%)
• Because of poor solubility of oxygen in water, only about 3% of O2
is transported by the plasma.
• Oxygen molecule combines loosely and reversibly with the heme
portion of haemoglobin to form oxyhaemoglobin
• When PO2 is high, as in the pulmonary capillaries, oxygen binds
with the hemoglobin, but when PO2 is low, as in the tissue
capillaries, oxygen is released from the haemoglobin
• Combination of oxygen with haemoglobin is only as a physical
combination, i.e. it is only oxygenation and not oxidation, so that it
can easily be released at the tissue.
• Haemoglobin combines with oxygen readily whenever the partial
pressure of oxygen in the blood is more, while it releases it
whenever the partial pressure of oxygen in the blood is less
• At the lungs, oxygen diffuse from alveoli into pulmonary
capillary and dissolve in plasma until PO2 rises to about
100mmHg.
• At equilibrium, plasma contain only 0.3mL of dissolved O2
per 100mL of total plasma O2
• Due to this high oxygen tension in the plasma, it diffuses
into the red blood cells and combine with haemoglobin
• Oxygen combines with the iron in heme part of
haemoglobin.
• Each molecule of haemoglobin contains 4 atoms of iron and
each atom of iron combines with one molecule of oxygen.
Thus, each molecule of Hb carries 4 molecules of oxygen
• Iron of the haemoglobin is present in ferrous form and after
combination with oxygen, iron remains in ferrous form only.
• One gram of Hb transport 1.34mL of oxygen. Thus, oxygen
carrying capacity of Hb is 1.34mL/g
• Oxygen carrying capacity of blood refers to the amount of oxygen transported
by blood.
• Blood contain about 15 g/dL of Hb.
• Since oxygen carrying capacity of hemoglobin is 1.34 mL/g, blood with 15 g/dL
of Hb should carry 20.1 mL/dL of oxygen (i.e. 20.1 mL of oxygen in 100 mL of
blood).
• But oxygen carrying capacity of blood is only 19 mL/dL because the
haemoglobin is not fully saturated with oxygen. It is only 95% saturated.
• Reaction of Hb with O2 can be represented thus;
– Hb4 + O2 ←→ Hb4O2
– Hb4O2 + O2 ←→ Hb4O4
– Hb4O4 + O2 ←→ Hb4O6
– Hb4O6 + O2 ←→ Hb4O8
• The above reaction is rapid, requiring less than 0.01 s. The deoxygenation
(reduction) of Hb4O8 at the tissue is also very rapid
• It is a self catalytic reaction. Formation of Hb4O2 is relatively slow, but once
formed, Hb4O2 catalyses the formation of Hb4O4 which occur at a faster rate,
an so on
• Thus, combination of the first heme in the Hb molecule with O2 increases the
affinity of the
• second heme for O2, and oxygenation of the second increases the affinity of
the third, and so on, so that the affinity of Hb for the fourth O2 molecule is
many times that for the first. This makes O2-Hb dissociation curve to have a
steep rise
 Oxygen-haemoglobin dissociation curve
• The most important factor that determines how much O2 binds to
hemoglobin is the PO2; the higher the PO2, the more O2 combines with
Hb
• If a graph of the percentage saturation of Hb is plotted against partial
pressures of O2, it gives a sigmoid shaped curve known as the oxygen-
haemoglobin dissociation curve
• The curve shows the degree of saturation of haemoglobin at different
partial pressures of oxygen. It demonstrates the relationship between
partial pressure of oxygen and the percentage saturation of hemoglobin
with oxygen. It explains hemoglobin’s affinity for oxygen.
• It demonstrates a progressive increase in the percentage of haemoglobin
bound with oxygen as blood PO2 increases (per cent saturation of
hemoglobin).
• Lower part of the curve indicates dissociation of oxygen from hemoglobin.
Upper part of the curve indicates the uptake of oxygen by hemoglobin
depending upon partial pressure of oxygen
• Because the blood leaving the lungs and entering the systemic arteries
usually has a PO2 of about 95 mm Hg, the usual oxygen saturation of
systemic arterial blood is about 97 percent.
• In normal venous blood returning from the peripheral tissues, the PO2 is
about 40 mm Hg, and the saturation of hemoglobin is about 75 percent.
• P50 is the partial pressure of oxygen at which
hemoglobin is 50% saturated with oxygen. It is
about 25 to 27 mm Hg
• At PO2 of 40 mm Hg, percentage saturation of
Hb is 75%. It becomes 95% when the partial
pressure of oxygen is 100 mm Hg.
Factors Affecting Oxygen-hemoglobin
Dissociation Curve
• Oxygen-hemoglobin dissociation curve is shifted
to left or right by various factors
• A shift to right indicates dissociation of oxygen
from haemoglobin
• A shift to left indicates acceptance (association)
of oxygen by haemoglobin
• Three important factors affect the oxygen–
hemoglobin dissociation curve:
– pH
– Temperature
– Concentration of 2,3-biphosphoglycerate (2,3-BPG),
also called 2,3-diphosphoglycerate (2,3-DPG)
• Factors that cause shift to the right:
– Decrease in pH
– Increased body temperature
– Decrease in partial pressure of oxygen
– Increase in partial pressure of carbon dioxide (Bohr effect)
– Excess of 2,3-BPG in RBC. 2,3-BPG is a byproduct in Embden-
Meyerhof pathway of carbohydrate metabolism. It combines
with β-chains of hemoglobin. It increases in conditions like
muscular exercise and in high attitude, so, the oxygen-
haemoglobin dissociation curve shifts to right to release more
O2.
• Factors that cause shift to the left:
– Increase in pH
– Decreased body temperature
– Increase in partial pressure of oxygen
– Decrease in partial pressure of carbon dioxide
– Presence of foetal haemoglobin. In foetal blood, because foetal
hemoglobin has more affinity for oxygen than the adult
haemoglobin
Bohr Effect
• Bohr effect is the effect by which presence of carbon
dioxide decreases the affinity of haemoglobin for
oxygen.
• In the tissues, due to continuous metabolic activities,
the partial pressure of carbon dioxide is very high and
carbon dioxide enters the blood
• Presence of carbon dioxide decreases the affinity of
haemoglobin for oxygen, and enhance further release
of oxygen to the tissues
• Shift of the oxygen-haemoglobin dissociation curve to
the right in response to increases in blood carbon
dioxide and hydrogen ions enhances the release of
oxygen from the blood in the tissues and oxygenation
of the blood in the lungs.

Bohr effect was postulated by Christian Bohr in 1904.

• As blood pass through the tissues, carbon dioxide
diffuses from the tissue into the blood, thus, increasing
the blood PCO2, which in turn raises the blood H2CO3
and the hydrogen ion concentration.
• These effects shift the oxygen-haemoglobin
dissociation curve to the right and downward, forcing
oxygen away from haemoglobin, and therefore
delivering increased amounts of oxygen to the tissues.
• In the lungs, the opposite effect occurs, where carbon
dioxide diffuses from the blood into the alveoli, there
by reducing the blood PCO2 and decreasing the
hydrogen ion concentration, shifting the oxygen-
haemoglobin dissociation curve to the left and upward,
causing more oxygen to bind with Hb.
Transport of CO2
• CO2 is transported in four ways:
– 1. As dissolved form: dissolved in plasma as solution.
Only 3mL/100mL (7%) is transported in this form
– 2. As bicarbonate (63%): From plasma, CO2 enters the
RBCs and combine with water to form carbonic acid
(in the presence of carbonic anhydrase). Almost all
carbonic acid (99.9%) then dissociates into
bicarbonate and hydrogen ions. The bicarbonate ions
diffuse through the cell membrane into plasma in
exchange for chloride (chloride shift/ Hamburger
phenomenon). Reverse chloride shift occurs in the
lungd. The hydrogen ions dissociated from carbonic
acid are buffered by hemoglobin inside the cell.
– 3. As carbamino compounds (30%). In combination
with Hb and plasma proteins
Hamburger phenomenon was discovered by Hartog
Jakob Hamburger in 1892
CO2 dissociation curve
• The amount of carbon dioxide combining with
blood depends upon the partial pressure of
carbon dioxide.
• Carbon dioxide dissociation curve is the curve
that demonstrates the relationship between
the partial pressure of carbon dioxide and the
quantity of carbon dioxide that combines with
blood.
Haldane Effect
• Haldane effect is the effect by which combination of oxygen with
hemoglobin displaces carbon dioxide from hemoglobin.
• Excess of oxygen content in blood causes shift of the carbon dioxide
dissociation curve to right.
• Due to the combination with oxygen, hemoglobin becomes strongly
acidic. It causes displacement of carbon dioxide from haemoglobin
because highly acidic hemoglobin has low tendency to combine
with carbon dioxide, so carbon dioxide is displaced from blood.
• Also, because of the acidity, hydrogen ions are released in excess.
Hydrogen ions bind with bicarbonate ions to form carbonic acid.
Carbonic acid in turn dissociates into water and carbon dioxide and
the carbon dioxide is released from blood into alveoli.
• Haldane effect is essential for release of carbon dioxide from blood
into the alveoli of lungs and also for uptake of oxygen by the blood.
Haldane effect was first described by John Scott
Haldane in 1860.
A

Exchange of O2 and CO2 in (A) pulmonary capillaries (external respiration)

and (B) systemic capillaries (internal respiration)
 CONTROL OF RESPIRATION

• Respiration is a reflex process, but it can be

controlled voluntarily for a short period of
time
• Respiration is controlled by two major
mechanisms, i.e. nervous and chemical
mechanisms
Nervous control of respiration
• The respiratory center is composed of several groups of
neurons located bilaterally in the medulla oblongata and
pons of the brain stem
• It is divided into three major collections
– (1) a dorsal respiratory group (inspiratory center), located in the
dorsal portion of the medulla, which mainly causes inspiration
– (2) a ventral respiratory group (expiratory center), located in the
ventrolateral part of the medulla, which mainly causes
expiration and
– (3) the pneumotaxic center (also called pontine respiratory
group), located dorsally in the superior portion of the pons,
which mainly controls rate and depth of breathing.

• The dorsal respiratory group of neurons plays the most

fundamental role in the control of respiration
Dorsal respiratory group
• Dorsal respiratory group of neurons are inspiratory neurons
situated in the nucleus of tractus solitarius present in the upper
part of the medulla oblongata
• Nucleus of tractus solitarius is the sensory termination of both the
vagal and the glossopharyngeal nerves, which transmit sensory
signals into the respiratory center from peripheral chemoreceptors,
baroreceptors and several types of receptors in the lungs.
• The basic rhythm of respiration is generated mainly in the dorsal
respiratory group
• During normal quiet breathing, neurons of the DRG send impulses
to the diaphragm via the phrenic nerves and the external intercostal
muscles via the intercostal nerves
• The diaphragm and external intercostals contract and inspiration
occurs.
• When the DRG becomes inactive after two seconds, the diaphragm
and external intercostals relax for about three seconds, allowing the
passive recoil of the lungs and thoracic wall. Then, the cycle repeats
itself.
The ventral respiratory group
• The ventral respiratory group of neurons are situated in
nucleus ambiguous and nucleus retroambiguous in the
medulla oblongata, anterior and lateral to the nucleus of
tractus solitarius.
• It has both inspiratory neurons in the central area of the
group, and expiratory neurons in the caudal and rostral
areas of the group.
• Normally, ventral respiratory group is inactive during quiet
breathing, but become active during forced breathing like
during exercise, when playing a wind instrument, or at high
altitudes.
• They stimulate accessory inspiratory and expiratory
muscles
• During forceful inhalation, nerve impulses from the DRG
activate neurons of the VRG involved in forceful inhalation
to send impulses to the accessory muscles of inhalation to
contract, which result in forceful inhalation.
• During forceful exhalation, neurons of the VRG
involved in forceful exhalation send impulses to the
accessory muscles of exhalation to contract, resulting
in forceful exhalation.
• The pre-Botzinger complex is a cluster of neurons
located in the VRG above the nucleus ambiguous and is
believed to be important in the generation of the
rhythm of breathing
• It receives sensory inputs form the nucleus of tractus
solitarius and projects excitatory signals to the
inspiratory neurons of the DRG and VRG and inhibitory
signals to the expiratory neurons of the VRG.
• It is composed of pacemaker cells that set the basic
rhythm of breathing
• The pacemaker cells send input to the DRG, driving the
rate at which DRG neurons fire action potentials
Pneumotaxic center
• A pneumotaxic center is located in the nucleus parabrachialis and
subparabrachial nuclei (also called ventral parabrachial or Kolliker-
Fuse nucleus) located in the dorsolateral part of reticular formation
in upper pons.
• It control the DRG by acting through apneustic center.
• It inhibits the apneustic center so that the dorsal group neurons are
inhibited, thus, stopping inspiration and starting expiration
• The pneumotaxic center, therefore, influences the switching
between inspiration and expiration. It increases respiratory rate by
reducing the duration of inspiration
• A strong pneumotaxic signal can increase the rate of breathing to
30 to 40 breaths per minute, whereas a weak pneumotaxic signal
may reduce the rate to only 3 to 5 breaths per minute.
• The Apneustic center
• Apneustic center is situated in the reticular formation of lower
pons. It increases depth of inspiration by acting directly on dorsal
group neurons
• It has an inherent tonic activity which stimulated the inspiratory
neurons of the DRG
Control of respiration from higher centers
(cerebral cortex)
• Though breathing is an involuntary action, it can be controlled voluntarily,
at least for some a short time due to voluntary impulses from cerebral
cortex, e.g. taking a deep breath, or holding the breath under water or due
to bad odour
• Higher centers alter respiration by sending impulses directly to dorsal
group of neurons.
• Impulses from anterior cingulate gyrus, genu of corpus callosum, olfactory
tubercle and posterior orbital gyrus of cerebral cortex inhibit respiration.
• Impulses from motor area of cerebral cortex cause forced breathing
• When breath is held for some time, CO2 and H+ build up in the body.
• When PCO2 and H concentrations increase to a certain level, the DRG are
strongly stimulated, and nerve impulses are sent along the phrenic and
intercostal nerves to inspiratory muscles, and breathing resumes, whether
the person likes it to or not
• Nerve impulses from the hypothalamus and limbic system also stimulate
the respiratory center, allowing emotional stimuli to alter breathing as, for
example, in laughing and crying
 Ondine’s curse
• Is a pathological condition in which the
nervous automatic breathing control is
paralyzed, while the voluntary control
system is retained.
• Person can stay alive only by staying awake
and remembering to breathe, or maintained
on mechanical respirator during sleep.
• This condition may develop in cases of
bulbar poliomyelitis (poliomyelitis of the
medulla oblongata) or due to compression
of the medulla.
Hering-Breuer Reflex
• Stretch receptors (baroreceptors) are located in the walls of
bronchi and bronchioles.
• When these receptors become stretched during
overinflation of the lungs, nerve impulses are sent along
the vagus nerves to the dorsal respiratory group (DRG)
• The DRG is inhibited and the diaphragm and external
intercostals relax. As a result, further inhalation is stopped
and exhalation begins.
• As air leaves the lungs during exhalation, the lungs deflate
and the stretch receptors are no longer stimulated.
• Thus, the DRG is no longer inhibited, and a new inhalation
begins.
• This inflation-deflation reflex is referred to as the Hering–
Breuer reflex
• It is a protective mechanism that prevents excessive
inflation of the lungs, for example, during severe exercise,
Proprioceptor Stimulation of Breathing
• At the beginning of exercising, the rate and depth
of breathing increase, even before changes in
PO2, PCO2, or H level occur.
• The main stimulus for these quick changes in
respiratory effort is input from proprioceptors,
which monitor movement of joints and muscles.
• Nerve impulses from the proprioceptors
stimulate the DRG.
• Axon collaterals (branches) of upper motor
neurons that originate in the primary motor
cortex (precentral gyrus) also feed excitatory
impulses into the DRG
• NB: respiratory centers are also affected by impulses from
baroreceptors, juxtacapillary (J) receptors in the wall of alveoli,
thermoreceptors, irritant receptors of the lungs, and pain receptors
Chemical control of respiration
• Chemical mechanism of regulation of respiration is
operated through the chemoreceptors.
• Chemoreceptors are sensitive to hypoxia (decreased O2
conc), hypercapnea (increased CO2 conc) and acidosis
(increased H+ conc/decrease pH)
• Chemoreceptors can be central chemoreceptors (in brain)
or peripheral chemoreceptors.
• Central chemoreceptors are situated in deeper part of
medulla oblongata, in close proximity and connected to the
DRG.
• They are in close contact with blood and cerebrospinal fluid
and are responsible for 70% to 80% of increased ventilation
through chemical regulatory mechanism.
• Main stimulant for central chemoreceptors is the increased
hydrogen ion concentration. Blood H+ cannot cross blood
brain barrier and blood-cerebrospinal fluid barrier.
• If carbon dioxide increases in the blood, it can easily cross
the blood brain barrier and blood cerebrospinal fluid
barrier and enter the interstitial fluid of brain or the
cerebrospinal fluid.
• There, the carbon dioxide combines with water to form
carbonic acid, which dissociates into hydrogen ion and
bicarbonate ion
• Hydrogen ions stimulate the central chemoreceptors.
• From chemoreceptors, the excitatory impulses are sent to
DRG, resulting in increased ventilation, and the excess
carbon dioxide is washed out and respiration is brought
back to normal
• Peripheral chemoreceptors are the chemoreceptors
present in carotid and aortic bodies and are stimulated
mainly by hypoxia.
• Aortic bodies are supplied by the vagus nerves, while the
carotid bodies are supplied by the glossopharyngeal nerves.
• Hypoxia cause stimulation of aortic and Hering
nerves which excite the DRG, resulting in
increased ventilation.
• This provides enough oxygen and rectifies the
hypoxia
• In addition to hypoxia, peripheral
chemoreceptors are also mildly stimulated by
hypercapnea and increased hydrogen ion
concentration.
 HYPOXIA
• Hypoxia = abnormal decreased oxygen in tissue
• Decreased blood supply to tissue = ischaemia
• Hypoxia can be
– hypoxic hypoxia
– anaemic hypoxia
– stagnant hypoxia or
– histotoxic hypoxia
• Hypoxic hypoxia is due to reduction in PO2 in arterial blood. It may caused
by inspiring low O2 air (e.g. in high altitude), decrease pulmonary
ventilation (e.g. in pneumothorax, paralysis of respiratory muscles, etc),
insufficient lung perfusion.
• In anaemic hypoxia, the oxygen carrying capacity of blood is decreased as
a result of anaemia, cyanide or CO poisoning
• Stagnant hypoxia is as a result of sluggish blood flow to tissue (e.g. due to
shock, haemorrhage, embolism/thrombosis or congestive heart failure)
• In histotoxic hypoxia, there is anability of the body cells to utilize O2
supplied to them due to cyanide or sulfide poisoning. These poisonous
substances destroy the cellular oxidative enzymes and there is a complete
paralysis of cytochrome oxidase system. So, even if oxygen is supplied, the
tissues are not in a position to utilize it.
 HYPERCAPNEA
• Hypercapnea is the increased carbon dioxide content of blood.
• „Hypercapnea occurs in conditions, which leads to blockage of respiratory pathway, as in case of
asphyxia.
• It also occurs while breathing the air containing excess carbon dioxide.
• During hypercapnea, the respiratory centers are stimulated excessively. It leads to dyspnea.
• The pH of blood reduces and blood becomes acidic.
• Hypercapnea is associated with tachycardia and increas ed blood pressure. There is flushing of skin
due
• to peripheral vasodilatation.
• The nervous system is also affected, resulting in headache, depression and laziness.
• Muscular rigidity, fine tremors and generalized convulsions.
• Finally, giddiness and loss of consciousness occur.

HYPOCAPNEA
• Hypocapnea is the decreased carbon dioxide content in blood.
• „Hypocapnea occurs in conditions associated with hypoventilation.
• It also occurs after prolonged hyperventilation, because of washing out of excess carbon dioxide
• It cause depression of respiratory centers, leading to decreased rate and force of respiration.
• The pH of blood increases, leading to respiratory alkalosis.
• Calcium concentration decreases. It causes tetany (neuromuscular hyperexcitability and carpopedal
spasm).
• Dizziness, mental confusion, muscular twitching and loss of consciousness also occur
 RESPIRATORY CHANGES IN EXERCISE

• ASSIGNMENT
 RESPITRATORY CHANGES IN HIGH ALTITUDE
• High altitude is the region of earth located at an
altitude of above 8,000 feet above sea level.
• When ascending to high altitude, atmospheric
pressure falls and the amount of air in the
environment decreases.
• PO2 and PN2 also fall proportionately
• Barometric pressure decreases to about
523mmHg at altitude of 10,000 feet above sea
level
• At 50,000 feet, it decreases further to 87 mm Hg.
• As the barometric pressure decreases, the
atmospheric oxygen partial pressure decreases
proportionately
• PO2 at sea level is 159 mm Hg, but at 50,000 feet, it
decreases to only 18 mm Hg
• Though amount of oxygen in the atmosphere is same
as that of sea level, PO2 decreases proportionately due
to decrease in barometric pressure
• This leads to hypoxia.
• When a person ascends to high altitude, especially by
rapid ascent, the various systems in the body cannot
cope with lowered oxygen tension and effects of
hypoxia start.
• In order to be able to survive at such an altitude, the
body has to acclimatize to the environment
• Acclimatization help the body to cope with adverse
effects of hypoxia at high altitude
• Acclimatization to high altitude include
– Increased pulmonary ventilation: Increase in pulmonary
ventilation is due to the stimulation of chemoreceptors
– Increased O2 Diffusing Capacity of The Lung: Due to increased
pulmonary blood flow and increased ventilation, diffusing
capacity of gases increases in alveoli. It enables more diffusion
of oxygen in blood
– Stimulation of Erythropoiesis: RBC count increases and packed
cell volume increases to about 59%. Hemoglobin concentration
rises to 20g/dL
– Circulatory/Cardiovascular Adjustments: vasodilatation, increase
in rate and force of contraction of the heart and increased
cardiac output. Increased cardiac output increases the
pulmonary blood flow and pressure, leading to pulmonary
hypertension that may be associated with right ventricular
hypertrophy
– Cellular Acclimatization: there is increase in number of
mitochondria and oxidation enzymes involved in metabolic
reaction, and also increase in vascularity in tissues
(angiogenesis)
– There is increase in 2,3 – DPG level which increase oxygen
delivery to tissues
Mountain sickness
• It is a condition characterized by adverse effects of hypoxia
at high altitude, usually in first timers.
• It occurs within a day in these persons, before they get
acclimatized to the altitude
• Symptoms include:
– Loss of appetite, nausea and vomiting
– Increase heart rate and force of contraction
– Increased pulmonary blood pressure results in pulmonary
edema, which causes breathlessness.
– Because of cerebral oedema, there is headache, depression,
disorientation, irritability, lack of sleep, weakness and fatigue.
Sudden exposure to hypoxia in high altitude causes
vasodilatation in brain, which leads to increased capillary
pressure and leakage of fluid from capillaries into the brain
tissues
• Symptoms of mountain sickness disappear by breathing
oxygen.
• Occasionally, a person who remains at high
altitude too long develops chronic mountain
sickness
• The red cell mass and haematocrit become
exceptionally high
• Pulmonary arterial pressure becomes too much
elevated more than that which occurs during
acclimatization,
• Right side of the heart becomes greatly enlarged
• Peripheral arterial pressure begins to fall
• Congestive heart failure ensues and death often
follows unless the person is removed to a lower
altitude.
 DEEP SEA DIVING
• Exposure to hyperbaric conditions (high ambient
pressure) occurs when one descends under water as
in diving or with descent in a caisson for underwater
construction work.
• In deep sea or mines, the barometric pressure
increases significantly.
• Increased pressure leads to compression on the
body and internal organs, and decrease in volume of
gases.
• For every 10m of depth under the sea, pressure
increases by 1 atm
• In order to prevent collapse of the lungs, the air
breathed by the diver must be supplied under high
pressure (hyperbaric air)
• Hyperbaric air contain oxygen, nitrogen and CO2
• As the diver descend further, the increased
pressure cause compression of inspired gases,
leading to decrease in volume and increase in
pressure.
• Increased pressure causes nitrogen and
oxygen to dissolve in body fluid
• As the depth increase, quantity of dissolved
gases increase
• At sea level, nitrogen is inert, but when
breathed at high pressure, it can cause
narcosis.
Nitrogen narcosis
• Narcosis = unconsciousness or stupor (lethargy with
suppression of sensations and feelings/sleepy state).
• Nitrogen narcosis is the narcotic effect produced by
nitrogen at high pressure.
• Under hyperbaric conditions, respiratory gases (O2, N2,
CO2) become toxic, particularly to the nervous system.
• Nitrogen is soluble in fat. During compression by high
barometric pressure in deep sea, nitrogen escapes from
blood vessels and gets dissolved in the fat present in
various parts of the body, especially the neuronal
membranes.
• Dissolved nitrogen acts like an anesthetic agent,
suppressing the neuronal excitability
• It is common in deep sea divers, who breathe
compressed air (air under high pressure).
• Breathing compressed air is essential for a deep
sea diver or an underwater tunnel worker, in
order to equalize the surrounding high pressure
that is threatening to collapse the lungs.
• Nitrogen narcosis is characterized by an altered
mental state, similar to alcoholic intoxication
• When a diver remains beneath the sea for an
hour or more and is breathing compressed air, at
about 120 ft, the first symptom of mild nitrogen
narcosis appears
• The diver becomes very jovial (marked euphoria),
careless and does not understand the seriousness of
the conditions.
• At 150 to 200 feet, the diver becomes drowsy.
• At 200 to 250 feet, he becomes extremely fatigued and
weak. There is loss of concentration and judgment.
Ability to perform skilled work or movements (manual
dexterity) is also lost.
• Beyond the depth of 250 ft (8.5 atmospheres
pressure), the person becomes unconscious.
• Features of nitrogen narcosis are similar to those of
alcoholic intoxication, hence, it is often called
“ruptures of the depths”
• There is loss of memory and impaired intellectual
functions.
• At greater depths manual dexterity is lost, there is
clumsiness, drowsiness and narcosis (sleepy state).
Oxygen toxicity
• Oxygen toxicity is the increased oxygen content in tissues,
beyond certain critical level.
• It occurs because of breathing pure oxygen with a high pressure
of 2 to 3 atmosphere (hyperbaric oxygen).
• The extremely high tissue PO2 that occurs when oxygen is
breathed at very high alveolar oxygen pressure can be
detrimental to many of the body’s tissues.
• If pure oxygen is breathed under pressure higher than 3 atm,
oxygen free radicals are formed in the tissues which include
superoxide free radical ‘O2- and hydrogen peroxide H2O2 which
are highly oxidizing agents.
• The agents oxidize the polyunsaturated fatty acids of the cell
membrane and the cellular enzymes systems causing severe
damage to the cells.
• Breathing oxygen at 4 atmospheres pressure of oxygen (PO2 =
3040 mm Hg) will cause brain seizures followed by coma within
30 to 60 minutes. The seizures often occur without warning and
are likely to be lethal to divers submerged beneath the sea.
• Other symptoms of acute O2 toxicity includes nausea, muscle
twitches, dizziness, visual disturbances, irritability, disorientation,
convulsion and coma
• At a pressure of 4 atm (30m depth) convulsions and coma occur in
about 30 minutes.
• The dangerous aspect of these symptoms is that they have rapid
onset
• In this condition, an excess amount of oxygen is transported in
plasma as dissolved form because oxygen carrying capacity of
hemoglobin is limited to 1.34 mL/g.
• Effects include
• Tracheobronchial irritation and pulmonary edema
• Metabolic rate increases in all the body tissues and the tissues are
burnt out by excess heat. Heat also destroys cytochrome system,
leading to damage of tissues.
• When brain is affected, first hyperirritability occurs. Later, it is
followed by increased muscular twitching, ringing in ears and
dizziness.
• Finally, the toxicity results in convulsions, coma and death.
Decompression sickness (Caisson diseases)
• Decompression sickness (a.k.a. dysbarism, compressed
air sickness, caisson disease, bends or diver’s palsy )is
the disorder that occurs when a person returns rapidly
to normal surroundings (sea level) from the area of
high atmospheric pressure like deep sea.
• High barometric pressure at deep sea leads to
compression of gases in the body, which reduces the
volume of the gases
• If one dives in water while breathing air, he is exposed
to high PN2. If he stays down for some time, large
volumes of N2 dissolve in body fluids (one litre of
nitrogen for each atmosphere). When nitrogen is
compressed by high atmospheric pressure in deep sea,
it escapes from blood vessels, enters the organs and
gets dissolved in the fat of the tissues and tissue fluids
(especially the brain tissues).
• On slow ascent up to the surface, N2 leaves the body
fluids to the blood, then to the lungs where it is
expired out in air.
• If the ascent was rapid “Decompression sickness”
occurs.
• Rapid ascent make N2 to leave the body fluids rapidly
and make nitrogen bubbles in the tissue fluids and
blood.
• The bubbles travel through blood vessels and ducts,
obstructing blood flow and produce air embolism,
leading to decompression sickness.
• As long as the person remains in deep sea, nitrogen
remains in solution and does not cause any problem.
• Decompression sickness also occurs in a person who
ascends up rapidly from sea level in an airplane
without any precaution
• Decompression sickness is characterized by:
– severe pain in tissues, particularly the joints (bends)
– Sensation of numbness, tingling or pricking (paresthesia) and
itching
– Temporary paralysis
– Muscle cramps associated with severe pain
– Coronary artery occlusion and coronary ischemia, caused by
bubbles in the blood
– Occlusion of blood vessels in brain and spinal cord
– Damage of tissues of brain and spinal cord because of
obstruction of blood vessels by the bubbles
– Dizziness, paralysis of muscle, shortness of breath and choking
– Fatigue, unconsciousness and death
• Decompression sickness is prevented by very slow ascent to
sea level, with short stay at regular intervals.
• Stepwise ascent allows nitrogen to come back to the blood,
without forming bubbles.
• If it occurs, it can be treated by hyperbaric oxygen therapy
• Decompression sickness can also be prevented by
using helium in the gas mixture instead of nitrogen
• Helium has only about one fifth the narcotic effect of
nitrogen, and only about one half as much volume of
helium dissolves in the body tissues as nitrogen, and
the volume that does dissolve diffuses out of the
tissues during decompression several times as
rapidly as does nitrogen, thus reducing the problem
of decompression sickness
• The low density of helium (one seventh the density
of nitrogen) keeps the airway resistance at a
minimum. Nitrogen is highly dense that airway
resistance can increase extremely, thus, increasing
the work of breathing even beyond endurance.
• SCUBA devise also minimize decompression sickness
SCUBA (self-contained underwater breathing apparatus)
• SCUBA is a devise used by deep sea divers and the
underwater tunnel workers, to prevent the ill effects
of increased barometric pressure in deep sea or
tunnels.
• This instrument can be easily carried and it contains
air cylinders, valve system and a mask.
• The SCUBA devise make it is possible to breathe air
or gas mixture without high pressure.
• Also, because of the valve system, only the amount
of air necessary during inspiration enters the mask
and the expired air is expelled out of the mask.
• Disadvantage of this instrument is that the person
using this can remain in the sea or tunnel only for a
short period. Especially, beyond the depth of 150
feet, the person can stay only for few minutes
 PRACTICE
• Which structures are part of the conducting zone of the respiratory
system?
• What functions do the respiratory and cardiovascular systems have in
common?
• How many lobes and secondary bronchi are present in each lung?
• How many lobes and secondary bronchi are present in each lung?
• Describe the location, structure, and function of the trachea.
• Describe the structure of the bronchial tree.
• Why are the right and left lungs slightly different in size and shape?
• State the types of cells that make up the wall of an alveolus and their
functions
• Exchange of respiratory gases occurs by diffusion across the respiratory
membrane, discuss
• Define and state the contents of bronchopulmonary segment?
• Describe the mechanism of breathing and muscles involved in breathing
• State and describe the following laws in relation to respiration
– Boyle’s law
– Dalton’s law
– Fick’s law
– Henry’s law
• Which of the following is NOT a function of the lungs?
A. Metabolism
B. Serves as a reservoir of blood
C. immunity
D. control of arterial blood pressure
E. none of the above
• How does the intra-pleural and intra-alveolar pressures change
during a normal, quiet breathing?
• Describe how alveolar surface tension, compliance, and airway
resistance affect breathing
• If you breathe in as deeply as possible and then exhale as much air
as you can, which lung capacity have you Demonstrated?
• Define FEV1
• State the factors that make oxygen to enter pulmonary capillaries
from alveoli and to enter tissue cells from systemic capillaries?
• Describe how the blood transports oxygen and carbon dioxide
• What is the most important factor that determines how much O2
binds to hemoglobin?
• As pH decreases or PCO2 increases, the affinity of haemoglobin for
O2 declines. Discuss
• Explain how exercise affects the oxygen-haemoglobin dissociation
curve and its benefit to the exercising person
• Is O2 more available or less available to tissue cells when you have
a fever? Why?
• How do temperature, H, PCO2, and 2,3-BPG influence the affinity of
Hb for O2?
• Which nerve convey impulses from the respiratory center to the
diaphragm?
• Describe the role of the following centers in breathing
– Dorsal respiratory group
– Ventral respiratory group
– Pontine respiratory group
• The peripheral chemoreceptors are most sensitive to
– A hypoxia
– B acidosis
– C hypercapnia
• An increase in arterial blood PCO2 stimulates
– A. the dorsal respiratory group
– B. the ventral respiratory group
– C. apneustic centre
• How do the cerebral cortex, levels of CO2 and O2, proprioceptors,
inflation reflex, temperature changes, pain, and irritation of the
airways modify breathing?
• On the summit of Mount Everest, where the barometric pressure is
about 250 mm Hg, the partial pressure of O2 is about
– A) 0.1 mm Hg.
– B) 0.5 mm Hg.
– C) 5 mm Hg.
– D) 50 mm Hg.
• The vital capacity is
– A) the amount of air that normally moves into (or out of) the lung with each
respiration.
– B) the amount of air that enters the lung but does not participate in gas exchange.
– C) the largest amount of air maximally expired after forced inspiration.
– D) the largest amount of gas that can be moved into and out of the lungs in 1 min.
• The tidal volume is
– A) the amount of air that moves into (or out of) the lung with each respiration.
– B) the amount of air that enters the lung but does not participate in gas exchange.
– C) the largest amount of air expired after maximal expiratory effort.
– D) the largest amount of gas that can be moved into and out of the lungs in 1 min.
• Which of the following is responsible for the movement of O2
from the alveoli into the blood in the pulmonary capillaries?
– A) active transport
– B) filtration
– C) secondary active transport
– D) facilitated diffusion
– E) passive diffusion
• Airway resistance
– A) is increased if the lungs are removed and inflated with saline.
– B) does not affect the work of breathing.
– C) is increased in paraplegic patients.
– D) is increased in asthma.
– E) makes up 80% of the work of breathing.
• Surfactant lining the alveoli
– A) helps prevent alveolar collapse.
– B) is produced by alveolar type I cells and secreted into the alveolus.
– C) is increased in the lungs of heavy smokers.
– D) is a glycolipid complex.
• Most of the CO2 transported in the blood is
– A) dissolved in plasma.
– B) in carbamino compounds formed from plasma proteins.
– C) in carbamino compounds formed from hemoglobin.
– D) as HCO3
• Which of the following has the greatest effect on the ability of blood to transport oxygen?
– A) hemoglobin concentration in the blood
– B) pH of plasma
– C) CO2 content of red blood cells
– D) temperature of the blood
• The main respiratory control center
– A) send out regular bursts of impulses to expiratory muscles during quiet respiration.
– B) is unaffected by stimulation of pain receptors.
– C) is located in the pons.
– D) send out regular bursts of impulses to inspiratory muscles during quiet respiration.
– E) is unaffected by impulses from the cerebral cortex.
• Intravenous lactic acid increases ventilation. The receptors responsible for this effect are located in
the
– A) medulla oblongata.
– B) carotid bodies.
– C) lung parenchyma.
– D) aortic baroreceptors.
– E) trachea and large bronchi
• Spontaneous respiration ceases after
– A) transection of the brain stem above the pons.
– B) transection of the brain stem at the caudal end of the medulla.
– C) bilateral vagotomy.
– D) bilateral vagotomy combined with transection of the brain stem at the superior border of the pons.
• The following physiologic events that occur in vivo are listed in random order:
– (1) decreased CSF pH;
– (2) increased arterial PCO2;
– (3) increased CSF PCO2;
– (4) stimulation of medullary chemoreceptors;
– (5) increased alveolar PCO2.
What is the usual sequence in which they occur when they affect respiration?
– A) 1, 2, 3, 4, 5
– B) 4, 1, 3, 2, 5
– C) 3, 4, 5, 1, 2
– D) 5, 2, 3, 1, 4
• Which of the following is the first branching of the bronchial tree that has gas exchanging
capabilities?
– A. Terminal bronchioles.
– B. Respiratory bronchioles.
– C. Alveoli
– D. segmental bronchi
• Which of the following is in the correct path of CO2 from the tissue to the atmosphere?
– A). Reaction with H2O to make H2CO3, dissociation to H+ and HCO3-, H+ combines with imidazole
side chain of hemoglobin, carried back to lungs as HHb+ and HCO3-, reverse reaction forms CO2.
– B). O2 is metabolized to CO2, reaction with H2O to make H2CO3, H2CO3 combines with imidazole
side chain of hemoglobin, H2CO3Hb+ is carried back to the lungs, reverse reaction forms CO2.
– C). Reaction with H2O to make H2CO3, dissociation to H+ and HCO3-, HCO3- combines with
imidazole side chain of hemoglobin, carried back to the lungs as HCO3-Hb+ and H+, reverse reaction
forms CO2.
– D). O2 is metabolized to CO2, reaction with H2O to make H2CO3, dissociation to H+ and HCO3-,
carried back to lungs in this form, reverse reaction forms CO2.
• Which of the following is TRUE at rest?
– A. TLC>VC>TV>FRC
– B. TLC>FRC>VC>TV
– C. TLC>VC>FRC>TV
– D. TLC>FRC>TV>VC
• Which of the following does NOT happen during inspiration?
– A. The ribs move upward.
– B. The diaphragm lifts up.
– C. The antero-posterior dimensions of the chest are increased.
– D. The tranverse dimensions of the thorax are increased.
• During inspiration, how does alveolar pressure compare to atmospheric
pressure?
– A. Alveolar pressure is greater than atmospheric.
– B. Alveolar pressure is less than atmospheric.
– C. Alveolar pressure is the same as atmospheric.
• Which of the following represents the pressure difference that acts to distend
the lungs?
– A. Alveolar pressure
– B. Airway opening pressure
– C. Transthoracic pressure
– D. Transpulmonary pressure
• If a patient had a progressive lung disease that required an
ever increasing pressure to fill the same volume of lung, how
would the lung's compliance be affected?
– A. It would increase it.
– B. It would stay the same.
– C. It would decrease it.