RESPIRATORY

PHYSIOLOGY
PART II
By
N.S Emmanuel PhD
 Diffusion of Gases
Oxygen and carbon dioxide move between air
and blood by simple diffusion, that is, from an
area of high to low partial pressure.

Fick’s law of diffusion states that the amount of

gas that moves across a sheet of tissue is
proportional to the area of the sheet but
inversely proportional to its thickness.
Area (A)
Diffusion constant (D), Difference
in partial pressure (P1 − P2),
Thickness (T).

As a result, carbon dioxide

diffuses more rapidly than does
oxygen.
Clinical Application of Fick’s Law
Clinically, Fick’s law is confirmed by the following general statements:
• The area (A) component of the law is verified in that a decreased alveolar
surface area (e.g., caused by alveolar collapse or alveolar fluid) decreases the
ability of oxygen to enter the pulmonary capillary
blood.
• The portion of the law is confirmed in that a decreased alveolar oxygen pressure
( or P1) (e.g., caused by high altitudes or alveolar hypoventilation) reduces the
diffusion of oxygen into the
pulmonary capillary blood.
• The thickness (T) factor is confirmed in that an increased alveolar tissue
thickness (e.g., caused by alveolar fibrosis or alveolar edema) reduces the
movement of oxygen across the alveolar-capillary
membrane.
DIFFUSING CAPACITY

Diffusing capacity is defined as the

volume of gas that diffuses through the
respiratory membrane each minute for a
pressure gradient of 1 mm Hg.
 DIFFUSING CAPACITY

Diffusing capacity for oxygen is 21

mL/minute/1 mm Hg.

Diffusing capacity for carbon dioxide is 400

mL/minute/1mm Hg.

Thus, the diffusing capacity for carbon dioxide

is about 20 times more than that of oxygen
Factors affecting DC:
1. Solubility of gases = directly
proportional to DC

2. Diffusing capacity is directly

proportional to pressure gradient.

Pressure gradient is the difference between

the partial pressure of a gas in alveoli and
pulmonary capillary blood
Factors affecting DC:

3. Diffusing capacity is directly proportional

to surface area of respiratory membrane.
Surface area of respiratory membrane in each
lung is about 70 sq m.
4. Diffusing capacity is inversely
proportional to molecular weight of the
gas. If the molecular weight is more, the
density is more and the rate of diffusion is
less.

5. Diffusion is inversely proportional to

the thickness of respiratory membrane
Limitations of Gas Transfer

Diffusion Coefficient.
Different gases behave differently.
Surface Area and Thickness of the alveolar wall.
Partial Pressure Gradient across the alveolar wall for
each individual gas.
Depends on both alveolar and mixed venous partial
pressure (start of capillary).
Factors affecting DC:

Diffusing capacity is decreased in

EMPHYSEMA in which many of the
alveoli are collapsed because of heavy
smoking or oxidant gases.
 RESPIRATORY EXCHANGE RATIO

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.
Whatever is absent is constant
 DIFFUSION OF GASES
159 mmHg
0.3 mmHg
TISSUE
Clinical conditions
that reduce rate
of gas diffusion
 TRANSPORT OF OXYGEN

1. As simple physical solution

2. In combination with hemoglobin.
Oxygen dissolves in water of plasma and is
transported

Amount of oxygen transported in this way is

very negligible. It is only 0.3 mL/100 mL of
plasma.

About 3% of total oxygen in blood.

Due to poor solubility of oxygen in water

content of plasma
In combination with Hb

Oxygen combines with hemoglobin in blood

and is transported as oxyhemoglobin (97%)

Oxygen Carrying Capacity of Hemoglobin

Oxygen carrying capacity of hemoglobin is the

amount of oxygen transported by 1 gram of
hemoglobin. It is 1.34 mL/g.
 OXYGEN-HEMOGLOBIN DISSOCIATION
CURVE
Gives insight into the relationship between pO2
and the percentage saturation of Hb with oxygen
(Affinity of Hb to oxygen)

Hemoglobin is saturated with oxygen only up to

95%.
Oxygen-hemoglobin dissociation curve

1. Shift to left indicates acceptance

(association) of
oxygen by hemoglobin
2. Shift to right indicates dissociation of
oxygen from
hemoglobin.
 Factors Affecting Oxygen-Hb Curve
Shift to right
i. Decrease in PO2
ii. Increase in PCO2(Bohr effect)
iii. Increase in H+ conc. Decrease in pH (acidity)
iv. Increased body temperature
v. Excess of 2,3-diphosphoglycerate (DPG)
in RBC.
Bohr’s Effect: presence of carbon dioxide
decreases the affinity of hemoglobin
for oxygen (Christian Bohr in 1904)
Bohr’s Effect
 pH
As the blood hydrogen-ion concentration increases
(decreased pH), the oxygen dissociation curve shifts to the
right. This mechanism enhances the unloading of oxygen at
the cellular level.

In contrast, as the blood hydrogen-ion concentration

decreases, the curve shifts to the left. This mechanism
facilitates the loading of oxygen onto hemoglobin as blood
passes through the lungs, because the pH increases as
carbon dioxide moves out of the blood and into the alveoli.
Temperature
As the body temperature increases, the curve moves to the
right. Thus, exercise, which produces an elevated
temperature, enhances the release of oxygen as blood flows
through the muscle capillaries.

Conversely, as the body temperature decreases, the curve

shifts to the left.

This mechanism partly explains why an individual’s lips, ears,

and fingers appear blue while swimming in very cold water.
That is, their is normal, but oxygen is not readily released
from the hemoglobin at the cold tissue sites.
Carbon dioxide
As the level increases (increased H+ concentration), the
oxyhemoglobin saturation decreases, shifting the
oxyhemoglobin dissociation curve to the right.

Decreasing levels (decreased H+ concentrations)

shift the curve to the left. The effect of and pH on the
oxyhemoglobin curve is known as the Bohr effect. The
Bohr effect is most active in the capillaries of working
muscles, particularly the myocardium.
 2,3-DPG
The RBCs contain a large quantity (about 15 mol/g Hb) of
the substance 2,3-diphosphoglycerate (2,3-DPG).

It is a metabolic intermediary that is formed by the RBCs

during anaerobic glycolysis.

Hemoglobin’s affinity for oxygen decreases as the 2,3-

DPG level increases. Thus, the effect of an elevated
concentration of 2,3-DPG is to shift the oxygen
dissociation curve to the right.
 Factors that influence 2,3-DPG
-Hypoxia: hypoxia increases the 2,3-DPG level

-Anaemia: The 2,3-DPG level increases as the

hemoglobin concentration decreases.

-pH: increases, the 2,3-DPG concentration increases

-Stored Blood: Blood stored for as little as 1 week has

been shown to have very low concentrations of 2,3-
DPG. Thus, when patients receive stored blood, the
oxygen unloading in their tissues may be reduced
because of the decreased 2,3-DPG level.
Fetal Hemoglobin
Fetal hemoglobin (HbF) is chemically different from
adult hemoglobin.

HbF has a greater affinity for oxygen and, therefore,

shifts the oxygen dissociation curve to the left (reducing
the P50).

During fetal development, the higher affinity of HbF

enhances the transfer of oxygen from maternal blood to
fetal blood. After birth, HbF progressively disappears
and is completely absent after about 1 year.
 Factors Affecting Oxygen-Hb Curve

Shift to Left
i. Increase in PO2
ii. Decrease in PCO2(Bohr effect)
iii. Decrease in H+ conc. Decrease in pH (acidity)
iv. Decreased body temperature
v. Reduction of 2,3-diphosphoglycerate
(DPG) in RBC.
Pulmonary Shunting: affects oxygen saturation
ASTHMA
•Allergies: Having allergies can raise your risk of developing asthma.

•Environmental factors: People can develop asthma after exposure to

things that irritate the airways. These substances include allergens,
toxins, fumes and second- or third-hand smoke. These can be especially
harmful to infants and young children whose immune systems haven’t
finished developing.

•Genetics: If your family has a history of asthma or allergic diseases, you

have a higher risk of developing the disease.

•Respiratory infections: Certain respiratory infections, such as

respiratory syncytial virus (RSV), can damage young children’s developing
lungs.
SABA/LABA= Short-acting Beta 2 agonist and Long-acting Beta 2 agonist respectively
Transport of Carbon Dioxide
Carbon dioxide is transported in the blood in four
ways:
1. As dissolved form (7%)
2. As carbonic acid (negligible)
3. As bicarbonate (63%)
4. As carbamino compounds (30%).
Hamburger phenomenon
Exchange of chloride
ion for a bicarbonate
ion across RBC
membrane.

It was discovered by
Hartog Jakob Hamburger
in 1892.
CARBON DIOXIDE DISSOCIATION CURVE

1. Shift to left indicates acceptance (association) of

oxygen by hemoglobin
2. Shift to right indicates dissociation of oxygen from
hemoglobin
Haldane Effect

Haldane effect is the effect by which combination of

oxygen with hemoglobin displaces carbon dioxide
from hemoglobin (In the LUNGS)

It was first described by John Scott Haldane in

1860. Excess of oxygen content in blood
causes shift of the carbon dioxide dissociation curve
to right.
Causes of Haldane Effect
1. Highly acidic hemoglobin has low tendency to
combine with carbon dioxide. So, carbon dioxide is
displaced from blood.

2. 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. Carbon dioxide is released from blood into
alveoli.
 ACID-BASE BALANCE AND REGULATION
Under normal conditions

Arterial pH range is 7.35 to 7.45.

Venous pH range is 7.30 to 7.40.

Alkalosis or alkalemia
When the pH of the arterial blood is greater than 7.45, B/cos of
excess amount of bicarbonate ions (HCO3)

Acidosis or acidemia
When the pH falls below 7.30
Blood has an excess amount of hydrogen ions.
Assignment
Discuss the production H+ ions in the body from these processes

(1) the breakdown of phosphorous-containing proteins (phosphoric

acid)

(2) the anaerobic metabolism of glucose (lactic acid)

(3) the metabolism of body fats (fatty and ketone acids)

(4) the transport of CO2 in the blood as HCO3 liberates Hydrogen

ions.
 Regulation of Breathing

Respiration is a reflex process. it can be

controlled voluntarily for a short period of about 40
seconds.
Regulation of Breathing
Nervous mechanism that
regulates the respiration
includes:
1. Respiratory centers
2. Afferent nerves
3. Efferent nerves. (Design
of communication)
The respiratory
center is located in
the medulla
oblongata and pons,
in the brainstem.

It is made up of
three major
respiratory groups of
neurons, two in the
medulla and one in
the pons.
Pontine centers and Medullary centers

Respiratory Group 1
Pneumotaxic center= (PNC)
Apneustic center = (APC)

Group 2 (DRG)= Dorsal resp. -

inspiration center

Group 3 (VRG) = Ventral resp.

and expiration center
Cerebral cortex (motor cortex-stimulatory)
Anterior cingulate gyrus,
Genu of corpus callosum,
Olfactory tubercle and
Posterior orbital gyrus

Regulation of voluntary Breathing

1. Dorsal resp. group (DRG)-Inspiration center
2. Ventral resp. group (VRG)-Expiration center

1. Ventral group has both

Insp. and Exp.
Neurons which
stimulate both
activities during forced
breathing.
 CHEMICAL MECHANISM

Chemical mechanism of regulation of respiration is

operated through the chemoreceptors.

Changes in Chemical Constituents of Blood which

Stimulate Chemoreceptors

1. Hypoxia (decreased pO2)

2. Hypercapnea (increased pCO2)
3. Increased hydrogen ion concentration .
Chemoreceptors are the sensory nerve endings,
which give response to changes in chemical
constituents of blood.
Chemoreceptors are classified
into two groups:

1. Central Chemoreceptors
2. Peripheral Chemoreceptors.
Central
chemoreceptors:
are situated in
deeper part of
MEDULLA
OBLONGATA,
close to the dorsal
respiratory group of
neurons.
Peripheral chemoreceptors
are present in CAROTID
and AORTIC region
Impulses from Higher Centers

Higher centers alter the 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 and Sylvian area of cerebral

cortex cause forced breathing
Impulses from Stretch Receptors of Lungs:
Hering-Breuer Reflex

protective reflex that restricts inspiration and

prevents overstretching of lung tissues. It is initiated
by the stimulation of stretch receptors of
air passage.

Reverse of this reflex is called Hering-Breuer

deflation reflex and it takes place during expiration.
During expiration, as the stretching of lungs is
absent, deflation occurs.
Hering-Breuer
Reflex
 Impulses from Baroreceptors
Baroreceptors are the receptors which give response to
change in blood pressure.

Baroreceptors in carotid sinus and arch of aorta give

response to increase in blood pressure.

Whenever arterial blood pressure increases,

baroreceptors are activated and send inhibitory impulses
to vasomotor center in medulla oblongata. This causes
decrease in blood pressure and inhibition of respiration
 ASSIGNMENT II

Read the Following

1. Cyanosis
2. Pneumonia
3. Pneumothorax
4. Emphysema
INTRODUCTION
Pulmonary function tests or lung function tests are
useful in assessing the functional status of the
respiratory system both in physiological and
pathological conditions.

Lung function tests are based on the measurement of

volume of air breathed in and out in quiet breathing
and forced breathing. These tests are carried out
mostly by using spirometer.
TYPES OF LUNG FUNCTION TESTS
Lung function tests are of two types:

1. Static lung function tests

2. Dynamic lung function tests.

Static Lung Function Tests (not rate dependent)

Static lung function tests are based on volume of air

that flows into or out of lungs. These tests do not
depend upon the rate at which air flows.
 Dynamic Lung Function Tests

Dynamic lung function tests are based on time,

i.e. the rate at which air flows into or out of
lungs. These tests include: forced vital capacity,
forced expiratory volume, maximum
ventilation volume and peak expiratory
flow.

Dynamic lung function tests are useful in

determining the severity of obstructive and
 Dynamic Lung Function Tests

Dynamic lung function tests are based on time,

i.e. the rate at which air flows into or out of
lungs. These tests include:

a. forced vital capacity

b. forced expiratory volume
c. maximum ventilation volume
d. peak expiratory flow.
LUNG VOLUMES

Static lung volumes are the volumes of air

breathed by an individual. Each of these
volumes represents the volume of air present
in the lung under a specified static
condition
Tidal volume • 500 mL

Inspiratory
reserve • 3,300 mL
volume

Expiratory
reserve • 1000 mL
volume

Residual Volume
(1, 200mL)
TIDAL VOLUME
Tidal volume (TV) is the volume of air
breathed in and out of lungs in a single normal
quiet respiration. It signifies the normal depth of
breathing

INSPIRATORY RESERVE VOLUME

Inspiratory reserve volume (IRV) is an
additional volume of air that can be inspired
forcefully after the end of normal inspiration.
EXPIRATORY RESERVE VOLUME
Expiratory reserve volume (EVR) is the
additional volume of air that can be expired out
forcefully, after normal expiration.

RESIDUAL VOLUME
Residual volume (RV) is the volume of air
remaining in lungs even after forced expiration.
Normally, lungs cannot be emptied completely
even by forceful expiration.
 Residual volume is significant because of
two
reasons:
1. It helps to aerate the blood in between
breathing and during expiration
2. It maintains the contour of the lungs
LUNG CAPACITIES
Static lung capacities are the combination of two
or more lung volumes.
Static lung capacities are of four types:
1. Inspiratory capacity
2. Vital capacity
3. Functional residual capacity
4. Total lung capacity.
INSPIRATORY CAPACITY

Inspiratory capacity (IC) is the maximum

volume of air that is inspired after normal
expiration (end expiratory position).
VITAL CAPACITY (VC)

Vital capacity (VC) is the maximum volume

of air that can be expelled out forcefully
after a deep (maximal) inspiration.
TOTAL LUNG CAPACITY

Total lung capacity (TLC) is the volume of air

present in lungs after a deep (maximal)
inspiration. It includes all the volumes.
FUNCTIONAL RESIDUAL CAPACITY

Functional residual capacity (FRC) is the

volume of air remaining in lungs after normal
expiration (after normal tidal expiration).
Functional residual capacity includes
expiratory reserve volume and residual volume.
Spirometer
Dynamic Lung Volume
Forced expiratory volume (FEV) is the
volume of air, which can be expired
forcefully in a given unit of time (after a
deep inspiration).

It is also called timed vital capacity or

forced expiratory vital capacity
(FEVC). It is a dynamic lung volume.
FEV1 = Volume of air expired forcefully in 1
second (83% of TVC)

FEV2 = Volume of air expired forcefully in 2

seconds (94% of TVC)

FEV3 = Volume of air expired forcefully in 3

seconds (97% of TVC)
SIGNIFICANCE OF DETERMINING FEV

FEV is used in diagnosis of respiratory

diseases considering it is decreased
significantly in some respiratory disease.

Obstructive diseases (asthma and

emphysema)
Restrictive respiratory diseases
(fibrosis of
Lungs)
 PEAK EXPIRATORY FLOW RATE
Peak expiratory flow rate (PEFR) is the
maximum rate at which the air can be expired
after a deep inspiration. (400 L/minute)
200 L/minute
(restrictive)

100 L/minute
(obstructive)

Primarily used to
differentiate them
Restrictive respiratory disease: difficulty in
inspiration. Expiration is not affected

Obstructive respiratory disease: difficulty

in expiration.
VENTILATION
In general, the word ‘ventilation’ refers to
circulation of replacement of air or gas in a space.
In respiratory physiology, ventilation is the rate at
which air enters or leaves the lungs. Ventilation in
respiratory physiology
is of two types:
1. Pulmonary ventilation
2. Alveolar ventilation
PULMONARY VENTILATION

Pulmonary ventilation is defined as the

volume of air moving 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).
ALVEOLAR VENTILATION
Alveolar ventilation is the amount of air
utilized for gaseous exchange every minute.
Alveolar ventilation is different from
pulmonary ventilation.
DEAD SPACE
Dead space is defined as the part of the
respiratory tract, where gaseous exchange
does not take place. Air present in the dead
space is called dead space air.
TYPES OF DEAD SPACE
Dead space is of two types:
1. Anatomical dead space
2. Physiological dead space.
Anatomical dead space extends from nose
up to terminal bronchiole.
Anatomical dead space: Volume of air inside
air passages down the respiratory
bronchioles

Alveolar dead space: Volume of air in the

inactive (Non functioning) alveolar

Physiological dead space: Anatomical dead

space + Alveolar dead space
 HIGH ALTITUDE
AND
SPACE PHYSIOLOGY
High altitude is the region of earth located at an altitude
of above 8,000 feet from mean sea level. People can
ascend up to this level, without any adverse effect.
The many physiological systems cannot handle the decreasing oxygen
tension when a person is exposed to high altitude, especially by fast ascent.

In addition to hypoxia, a few other elements are partly to blame for the
modifications to how the body at a great height.

Factors affecting Physiological Fxtn @ High Altitude

 Hypoxia
Hypoxia is a state in which oxygen is
not available in sufficient amounts at
the tissue level to maintain adequate
homeostasis;
 CLASSIFICATION AND CAUSES
OF HYPOXIA
Four important factors which leads to hypoxia
are:
1. Oxygen tension in arterial blood
2. Oxygen carrying capacity of blood
3. Velocity of blood flow
4. Utilization of oxygen by the cells
 TYPES OF HYPOXIA
1. Hypoxic hypoxia
2. Anemic hypoxia
3. Stagnant hypoxia
4. Histotoxic hypoxia
Each type of hypoxia may be acute or chronic.
Simultaneously, two or more types of hypoxia may be
present.
 1. Hypoxic Hypoxia
Hypoxic hypoxia is caused by four factors
i. Low oxygen tension (atmospheric)
ii. Respiratory disorders (decreased pulmonary
Ventilation)
iii. Respiratory disorders
iv. Cardiac disorders
 2. Anemic Hypoxia
Anemic hypoxia is the condition characterized by the
inability of blood to carry enough amount of
oxygen. Oxygen availability is normal. But the blood is
not able to take up sufficient amount of oxygen due
to anemic condition.
 Causes
Any condition that causes anemia can cause anemic
hypoxia. It is caused by the following conditions:
i. Decreased number of RBCs
ii. Decreased hemoglobin content in the blood
iii. Formation of altered hemoglobin
iv. Combination of hemoglobin with gases other than
oxygen and carbon dioxide.
 3. Stagnant Hypoxia
Stagnant hypoxia is the hypoxia caused by decreased
velocity of blood flow. It is otherwise called hypokinetic
hypoxia.
 Causes
i. Congestive cardiac failure
ii. Hemorrhage
iii. Surgical shock
iv. Vasospasm
v. Thrombosis
vi. Embolism.
 4. Histotoxic Hypoxia
Histotoxic hypoxia is the type of hypoxia produced by
the inability of tissues to utilize oxygen.
Causes for histotoxic hypoxia
Histotoxic hypoxia occurs due to cyanide or sulfide
poisoning.
These poisonous substances destroy the cellular
oxidative enzymes and there is a complete paralysis of
cytochrome oxidase system.

Thus, even if oxygen is supplied, the tissues are not

in a position to utilize it.
 EFFECTS OF EXPANSION OF GASES
ON THE BODY

Volume of gases increases when the barometric

pressure is reduced.

At high altitude, due to the decreased barometric

pressure, volume of all gases increases in atmospheric
air, as well as in the body
 Expansion of gases in GI tract causes painful
distention of stomach and intestine. It is minimized by
supporting the abdomen with a belt or by evacuation of
the gases. Expansion of gases also destroys the alveoli.

During very rapid ascent from sea level to over 30,000

feet height, the gases evolve as bubbles, particularly
nitrogen, resulting in decompression sickness. Refer
 Nitrogen is present about 3.3 percent
weight of the human body.

It is found in many organic molecules,

comprising the amino acids that make up
proteins, and the nucleic acids that make up
DNA, enzymes, and hormones.
 EFFECTS OF LIGHT RAYS
Skin becomes susceptible for injury due to
many
harmful rays like ultraviolet rays of sunlight.

Sunrays reflected by the snow might

injure the
retina of the eye, if it is not protected with
suitable tinted glasses.
 MOUNTAIN SICKNESS

Mountain sickness is the condition characterized by

adverse effects of hypoxia at high altitude.

It is commonly developed in persons going to high

altitude for the first time.

It occurs within a day in these persons, before they get

acclimatized to the altitude.
1. Digestive System
Loss of appetite, nausea and vomiting occur because of
expansion of gases in GI tract.
2. Cardiovascular System
Heart rate and force of contraction of heart increases.
3. Respiratory System
Pulmonary blood pressure increases due to increased blood
flow. Blood flow increases because of vasodi­latation
induced by hypoxia. Increased pulmonary blood pressure
results in pulmonary edema, which cause breathlessness.
4. Nervous System
Symptoms
headache depression, disorientation, irritability, lack of sleep
weakness and fatigue.
These symptoms are developed because of cerebral edema.
Sudden exposure to hypoxia in high altitude causes
vasodilatation in brain.

Autoregulation mechanism of cerebral blood flow fails to

cope with hypoxia. It leads to an increased capillary pressure
and leakage of fluid from capillaries into the brain tissues.
ACCLIMATIZATION
Acclimatization refers to the adaptations or the adjustments
by the body in high altitude.

While staying at high altitudes for several days to several

weeks, a person slowly gets adapted or adjusted to the low
oxygen tension, so that hypoxic effects are reduced. It enables
the person to ascent further.