2. Respiration
Act of breathing resulting in exchange of
oxygen & CO2 b/w body tissues and
atmosphere
Divisions
◦ 4 main divisions
Pulmonary ventilation
Inflow & outflow of air b/w atmosphere & lung
alveoli
Diffusion
Of oxygen & CO2 b/w alveoli & blood
3. Transport
Of oxygen & CO2 in blood and body fluids to
& from cells
Regulation
Of ventilation & other acts of respiration
Functions of respiration
◦ Supply of oxygen to tissues & removal of CO2
from blood
◦ Helps in regulating acid base balance by
adjusting CO2 elimination from body
◦ Helps in keeping constant condition of water in
body through elimination of excess water vapors
◦ Eliminates certain harmful volatile substances
from body e.g. ammonia, alcohol etc
4. Mechanics of respiration
Lungs can be expanded & contracted in
2 ways;
◦ By downward & upward movement of
diaphragm to lengthen or shorten chest
cavity
◦ By elevation & depression of ribs to increase
& decrease anteroposterior diameter of chest
cavity
Inspiration & muscles of inspiration
◦ During inspiration (in normal quiet breathing);
main role is played by contraction of diaphragm that
pulls lower surfaces of lungs downward
6. Lungs pressure
Pleural pressure
◦ Pressure in narrow space b/w lung pleura &
chest wall pleura
◦ Negative pressure which prevents collapse of
lungs
◦ Also called lung recoil pressure
◦ Value; 5 cm of H2O
Alveolar pressure
◦ Pressure inside lung alveoli
◦ Different during inspiration & expiration
◦ Inspiration – alveolar pressure becomes -1 cm of
H2O
which causes air to move into lungs
7. ◦ Expiration – alveolar pressure rises to about
+1 cm of H2O
this forces inspired air out of lungs
Transpulmonary pressure
◦ Difference b/w alveolar pressure & pleural
pressure
◦ Pressure difference b/w alveoli & outer
surface of lungs
◦ Actually it is measure of recoil pressure
Recoil pressure
◦ Elastic forces in lungs that tend to collapse
lungs at each point of expansion
8. Pulmonary volumes
Tidal volume
◦ Volume of air inspired or expired with
each normal breath
◦ Value: 500 ml
Inspiratory reserve volume
◦ Extra volume of air that can be inspired in
after normal tidal volume
◦ Value: 3000 ml
9. Expiratory reserve volume
◦ Extra amount of air that can be expired by
forceful expiration after end of normal tidal
expiration
◦ Value: 1100 ml
Residual volume
◦ Volume of air still remaining in lungs after
most forceful expiration
◦ Value: 1200 ml
10. Pulmonary capacities
Combination of two or more pulmonary
volumes
Inspiratory capacity
Combination of tidal volume & inspiratory
reserve volume
Formula: I.C = T.V + IRV
Significance
This is the amount of air that a person can
breath;
◦ beginning at normal expiratory level & ending at
maximum lung distension
Value: 3500 ml
11. Functional residual capacity
Combination of expiratory volume &
residual volume
Formula: FRC = ERV + RV
Significance
This is amount of air remaining in lungs
at end of normal expiration
Value: 2300 ml
Vital capacity
Combination of inspiratory reserve
volume, tidal volume & expiratory
reserve volume
Formula: VC = IRV + TV + ERV
12. Maximum amount of air that a person
can expel from lungs;
◦ after first filling lungs to their maximum extent
& then expiring to maximum limit
Total lung capacity
Combination of vital capacity & residual
volume
Formula: TLC = VC + RV
Significance
Maximum volume to which lungs can be
expanded with greatest possible
inspiratory effort
Value: 5800 ml
13. Composition of inspired,
expired & alveolar air
Lungs can never be completely emptied of air b/c
of residual volume
The Relative Composition (% by Volume) of
Inspired, Expired & Alveolar Air
Gas
Inspired air
%
Expired air
%
Alveolar air
%
Oxygen 20.71 14.6 13.2
Carbon
dioxide
0.04 3.8 5.0
Water
vapour
1.25 6.2 6.2
Nitrogen 78.0 75.4 75.6
14. Inspired air contains approximately 21% by
volume of oxygen gas
As this fresh air is drawn into alveoli;
◦ it mixes with air already present (residual
volume)
Residual volume dilutes fresh air, so
oxygen content falls
CO2 content of alveolar air increases
significantly as gas exchange proceeds
◦ & CO2 diffuses from blood into alveoli
15. Oxygen content of expired air is higher than
that in alveoli
◦ This is explained by fact that expired air from
alveoli mixes with dead space air whose oxygen
content is same as that of atmosphere
CO2 content in expired air is less than that
of alveolar air
◦ explained by fact that expired air from alveoli
mixes with dead space air containing very low
levels of carbon dioxide
16. Water vapour content of expired air is
significantly higher than that of inspired air
◦ as air is breathed into alveoli, water from lining of
alveoli evaporates into alveolar air such that
expired air is greater in volume than inspired air
Nitrogen gas is neither used or produced by
body and actual amounts of nitrogen in
inspired an expired air do not change
◦ slightly larger volume of expired air means that
nitrogen forms part of larger volume during
expiration and so its % by volume decreases
17. There are several reasons for alveolar air
differences
◦ First, alveolar air is only partially replaced by
atmospheric air with each breath
◦ Second, oxygen is constantly being absorbed
into pulmonary blood from alveolar air
◦ Third, carbon dioxide is constantly diffusing from
pulmonary blood into alveoli
◦ Fourth, dry atmospheric air that enters
respiratory passages is humidified even before it
reaches alveoli
18. Transport of O2 & CO2 in Blood
& body fluids
O2 is transported in combination with Hb to tissue
capillaries
CO2 also combines with chemical substances in
blood that increases its transport to lungs
Whole transport of O2 in blood can be divided
into following steps;
1. Diffusion of O2 from alveolus into
pulmonary blood
Partial pressure of gaseous O2 in alveolus is
104 mmHg
◦ while PO2 in venous blood entering capillary is only
40 mmHg
19. Thus, due to pressure difference of 64
mmHg;
◦ O2 diffuses from alveolus into pulmonary
blood
In exercise
◦ During strenuous exercise body require as
much as 20 times normal amount of oxygen;
◦ This increase in O2 demand is met by;
Diffusing capacity for oxygen increases three folds
during exercise
Increased number of capillaries open in exercise
Dilatation of alveoli & capillaries
20. 2. Transport of oxygen in arterial blood
About 98% of blood coming from lung
has partial pressure of O2 about 104
mmHg
◦ while remaining 2% of blood, which comes
from bronchial vessels, comprises of venous
blood;
has PO2 of 40 mmHg (equal to that of normal
venous blood)
◦ Mixing of these two bloods in left atrium
makes final partial pressure of O2 about 95
mmHg
◦ This blood is then pumped by aorta into
21. 3. Diffusion of O2 from capillaries into
interstitial fluid
PO2 in interstitial fluid is 40 mmHg;
◦ while oxygenated blood has PO2 of about 95 mmHg
◦ This difference in O2 conc. causes diffusion of O2
from capillaries into interstitial fluid
Depends upon 2 factors
◦ Rate of tissue blood flow
◦ Rate of tissue metabolism
4. Diffusion of O2 from interstitial spaces into
cells
Normal intracellular PO2 – approx. 23 mmHg;
◦ b/c only 1-3 mmHg of O2 is normally required by cells
◦ Thus pressure difference causes O2 to diffuse into
cells
22. 5. Diffusion of CO2 from cells into
interstitial fluid
PCO2 inside cell is 46 mmHg;
◦ while in interstitial is 45 mmHg
◦ Pressure difference causes CO2 to diffuse out
from cells into interstitial fluid
6. Diffusion of CO2 from interstitial fluid
into capillaries
PCO2 in interstitial fluid is 45 mmHg;
◦ while in arterial end of capillary PCO2 is 40
mmHg
◦ Due to this pressure difference in PCO2, CO2
diffuses from interstitial fluid into capillaries
23. 7. Diffusion of CO2 from pulmonary blood
into alveolus
PCO2 of venous blood entering pulmonary
capillaries is 45 mmHg;
◦ while PCO2 of alveolar air is only 40 mmHg;
◦ Thus, only 5 mmHg pressure difference causes
all required CO2 diffusion out of pulmonary
capillaries into alveoli
◦ Finally CO2 from alveolus is exchanged
24. TRANSPORT OF O2 IN BLOOD
About 97% of O2 transported from lungs to tissues
is carried in combination with Hb in RBCs
Remaining 3% of O2 is carried in dissolved state in
water of plasma & cells
Oxygen-hemoglobin dissociation curve
When PO2 is high (lungs) O2 binds with Hb
But when PO2 is low (tissues) O2 is released from
Hb
◦ This relationship b/w PO2 & amount of oxygenation and de-
oxygenation of Hb is called Oxygen-Hb dissociation curve
26. Value of O2-Hb combinations
◦ Normal conc. of Hb – 15 gm/100ml of blood
◦ Normal amount of O2 carried by 1 gm of Hb –
1.34 ml of O2
◦ Max. amount of O2 carried by 100 ml of blood
– 20 ml of O2
Percentage of Hb bound with O2 –
known as percent saturation of Hb
Amount of O2 released by Hb
During normal conditions about 5 ml of
O2 is carried to tissues in each 100 ml of
blood
27. Amount of O2 released by Hb during
exercise
During strenuous exercise three times as
much O2 is transported in each 100 ml of
blood
◦ i.e. 15 ml O2 / 100 ml blood
Utilization coefficient
Percentage of blood that gives up O2 as
it passes through tissue capillaries
◦ Normally 25% of blood, gives up its O2 to
tissues
◦ During strenuous exercise – 75-85% or all
blood can give up its O2
28. Physiological significance of O2-Hb
dissociation curve
Sigmoid shape of curve is of great physiological
significance
◦ b/c it ensures that oxygenation & de-oxygenation of
Hb takes place in most optimum way
In lungs
At PO2 of 104 mmHg in alveolar air – more than
97% of Hb becomes saturated with O2
Even at PO2 of 60 mmHg – percent saturation of
Hb is 89%
So in any condition associated with fall in
alveolar PO2;
◦ appreciable amount of Hb can still be saturated
29. In tissues
A drop of PO2 from 100 to 50 mmHg would
release only 18% of O2
◦ while drop from 50 to 0 mmHg – release 75-85% of
O2
Significance of this phenomenon is supply of
more O2 to tissues during exercise where PO2 is
much lowered
Metabolic use of O2 by cells
Depends on following factors
◦ Intracellular PO2
◦ Distance of cells from capillaries
◦ Blood flow of tissues
30. Combination of Hb & CO
CO combines with Hb at same point as
does O2 – but 250 times more rapidly than
O2
The condition in which CO binds with Hb &
displaces O2 – termed as CO poisoning
31. Shift of O2-Hb dissociation curve
Shifting of curve to right
Indicates that Hb has decreased affinity for
oxygen
This makes it more difficult for Hb to bind to
oxygen
◦ requiring higher PO2 to achieve same oxygen
saturation
Rightward shift – increases PO2 in tissues
when it is most needed;
◦ such as during exercise
Causes
◦ Increase H+ conc. or decreased pH
◦ Increased CO2 conc.
◦ Increased temp.
◦ Increased diphosphoglycerate
32.
33. Shifting of curve to left
Left shift of curve is sign of hemoglobin's
increased affinity for oxygen
◦ e.g. at the lungs
Causes
◦ Decrease H+ conc. or decreased pH
◦ Decreased CO2 conc.
◦ Decreased temp.
◦ Decreased diphosphoglycerate
◦ CO poisoning
◦ Decreased metabolism
34. TRANSPORT OF CO2 IN BLOOD
Under normal resting condition;
◦ an avg; of 4 ml of CO2 is transported from tissue
to lungs in each 100 ml of blood
Forms of CO2 transport
1. Transport of CO2 in dissolved state
About 7% of CO2 – transported as dissolve
CO2
◦ Arterial blood content – 2.4 ml of CO2 / 100 ml
◦ Venous blood content – 2.7 ml of CO2 / 100 ml
◦ Thus 0.3 ml – transported in dissolved state in
each 100 ml of blood
35. 2. Transport of CO2 as carbamino compounds
30% of CO2 – transported in combination with
Hb & plasma proteins
Comprises transport of 1.5 ml of CO2 / 100 ml
of blood
CO2 combines with NH2 groups of blood
proteins to form unstable carbamino
compounds
Mostly CO2 combines with Hb forming
carbamino-Hb
◦ Since de-oxygenated Hb has more affinity for
CO2;
◦ so in tissues when Hb is reduced – deoxy Hb is
formed, which facilitates CO2 to lungs
36. 3. Transport of CO2 as bicarbonate ions
70% of CO2 is carried as bicarbonate ions
HCO3 ions are formed in RBCs & to lesser
extent in plasma
This transport comprises 2.2 ml of CO2 / 100
ml of blood
Chloride shift
Bicarbonate ions formed in RBCs diffuse out
into plasma
To maintain electrical neutrality of RBCs;
◦ an equal number of chloride ions diffuse into
cells from plasma
◦ This is known as chloride shift
37. CO2 dissociation curve
This curve predicts relationship b/w
quantity of CO2 present in blood in all
forms & PCO2
◦ i.e. dependence of total blood CO2 on Pco2
Haldane effect
An increase in CO2 in blood will cause
O2 to be displaced from Hb
◦ This phenomenon is known as Haldane
effect
Respiratory exchange ratio
Ratio of CO2 output to O2 uptake
◦ R = rate of CO2 output / rate of O2 uptake
38. Regulation of respiration
Respiratory center
Composed of several widely spread groups
of neurons in brain
Located in medulla oblongata & pons
Divisions
◦ 4 major parts
1. Dorsal respiratory group
Location
◦ In dorsal portion of medulla within nucleus of
tractus solitarius
39. Connections
◦ Nucleus of tractus solitarius receive sensory
signals via vagus & glassopharyngeal from
peripheral chemoreceptors & baroreceptors
Functions
Responsible for generating repetitive bursts
of inspiratory action potential
Generate inspiratory Ramp signals
During inspiration – signals for contraction of
inspiration begins very weakly at first
Then increases steadily in ramp fashion for about 2
sec
Abruptly ceases in next 3 sec & then begins again
This inspiratory signal is known as ramp signal
40. 2. Pneumataxic center
Location
◦ Dorsally in nucleus parabrachialis of upper
pons
Connections
◦ Serves as input source for inspiratory area
Functions
Transmits impulses continuously to
inspiratory area to control switch off point of
inspiratory ramp
Thus controls duration of inspiration
Can increase heart rate (up to 30-40 breaths
per min)
41. 3. Ventral respiratory group
Location
◦ In ventral medulla found in nucleus ambigus &
nucleus retroambigus
Functions
Works when more than normal ventilation is
required – thus it activates to increase respiratory
rate
Some part of it may also cause inspiration
Provides powerful expiratory signals to
abdominal muscles during expiration
4. Apneustic center
Location
◦ In lower pons
42. Connections
◦ Serves as input drive to dorsal respiratory group
Functions
Sends signals to dorsal respiratory group of
neurons to prevent Switch-off of inspiratory ramp
signal
Controls depth of respiration
Hering breuer inflation reflex
◦ This reflex is started when lungs become
overstretched
◦ Stretch receptors located in walls of bronchi &
bronchioles transmit signals via vagi into dorsal
respiratory group
◦ This switches off inspiratory ramp, stops further
inspiration & thus increases rate of inspiration
43.
44. Control of respiration
◦ Overall control divided into;
A. Chemical regulation
B. Nervous regulation
A. Chemical regulation
Respiration – maintain proper conc. of O2, CO2 &
H+ ions in tissues
◦ so highly responsive to changes in these, i.e.,
◦ excess of CO2
◦ change in H+
◦ lack of O2
Chemosensitive area
Location
◦ Lies bilaterally beneath ventral structure of medulla
45. Functions
◦ Highly sensitive to changes in blood CO2 & H+
ion conc.
◦ Increases rate & depth of respiration by
increasing intensity of inspiratory ramp signals
Excess of CO2
◦ Changes of CO2 in blood
◦ Excess of CO2 – most important factor b/c it can
cross blood brain barrier
It does this by reacting with water of tissues to form
carbonic acid
This in turn dissociates into H & bicarbonate ions
◦ H+ ions have potent direct stimulatory effect on
chemosensitive area to increase rate & depth of
respiration
46. ◦ Changes in CSF PCO2
◦ Changing PCO2 in CSF itself has more rapid
excitation of chemosensitive area
b/c CSF has very little protein & acid base buffers
◦ Therefore H+ ion conc. increases almost instantly
when CO2 enters CSF from brain vessels
B. Nervous regulation of respiration
Various mechanisms of regulation;
1. Chemoreceptors
2. Hering Breuer Reflex
3. Impulses from higher centers
4. Impulses from vasomotor center
5. Effect of temp
47. 1. Chemoreceptors
Nature
◦ Special type of nervous chemical receptors
Location
◦ Located in;
Carotid bodies
Aortic bodies
Other arteries of thorax & abdomen
◦ Carotid bodies
◦ Located bilaterally in bifurcation of common
carotid arteries
◦ Their afferent nerve fibers pass through Hering’s
nerves to glassopharyngeal nerves
◦ & then to dorsal respiratory area
48. ◦ Aortic bodies
◦ Located along arch of aorta
◦ Their afferent nerve fibers pass through vagi
to dorsal respiratory area
◦ Note; chemoreceptors are exposed at all
times to arterial blood, not venous blood
◦ Their partial pressure of O2 is same as PO2
of arterial blood
◦ Basic mechanism
Chemoreceptors are important for detecting
changes in O2, CO2 & H+ in blood
Have glandular cells – act as chemoreceptors &
stimulate nerve endings
49. Chemoreceptors – stimulated by changes in
arterial PO2 range of 60 & 30 mmHg
Effect of CO2 & H+ on chemoreceptors
◦ Increase in CO2 & H+ - excites chemoreceptors
◦ But their direct effect on respiratory center stimulation
is more powerful then their effect mediated through
chemoreceptors
2. Hering Breuer Reflex
◦ Control rhythm & depth of respiration
◦ Stretch receptors present in tracheo-bronchial tree
probably at point of bronchial branching
◦ As lung expand during act of respiration
impulses are carried to apneustic center which inhibits
discharge of inspiratory center
50. So act of inspiration ceases & expiration follows
“Hering-Breuer Inflation Reflex”
◦ During forced deflation of lungs – respiration may
be stimulated “Hering Breuer Deflation reflex”
3. Impulses from higher centers
◦ Emotional activities modify breathing;
◦ e.g., fear, anxiety, rage stimulates breathing
◦ In Shock – respiration depressed
4. Afferent impulses from sensory
receptors
◦ Painful stimuli stimulate respiratory center
◦ Newborn child doesn’t breath usually, but starts
breathing after slap
◦ Bucket full of water thrown on man causes gasp
& stimulated breathing is found
51. 5. Impulses from vasomotor center & effect
of BP on breathing
◦ Vasomotor center directly excites respiratory
center
This effect brought about by baroreceptors located in
carotid & aortic arch which are very sensitive to changes
in BP
◦ Baroreceptors – stimulated when there is rise in
BP
◦ They sends impulses to cardiac center,
vasomotor center & respiratory center
These impulses are inhibitory in nature
◦ Thus as BP rise, heart slows down (Marey’s
reflex) & respiration depressed
◦ So rise in BP will depress breathing & vice versa
52. 6. Effect of temp
◦ Increase in temp increases rate of respiration
◦ Hypothalamus initiates cascade of neurogenic
reactions;
to decrease body temp by increasing rate of respiration
◦ This facilitates loss of heat from body through
water vapours in expired air
53. Regulation of respiration during exercise
In strenuous exercise, O2 consumption & CO2
formation can increase as much as 20 folds
During exercise arterial PO2, PCO2 & pH all
remain almost normal
Following factors increases respiration during
exercise
Brain, on sending impulses to exercising muscles
also transmits collateral impulses to brain stem to
excite respiratory center according to need of body
During exercises body movements are believed to
increase pulmonary ventilation;
by exciting joint proprioceptors which in turn excite
respiratory center in brain
54. Hypoxia developing in muscles during exercise
elicits afferent nerve signals to respiratory center
to excite respiration
Many experiments suggest that brains ability to
increase ventilatory response during exercise is
mainly “learned response”
55. Specific pulmonary
abnormalities
Emphysema
◦ An increase in size of alveoli, either due to
dilatation or destruction of their walls
Pneumonia
◦ Any inflammatory condition of lung in which
some or all of alveoli are filled with fluid & blood
cells
◦ Results in two pulmonary abnormalities;
Reduction in total available surface area of respiratory
membrane
Decreased ventilation-perfusion ratio
◦ Causes
Bacteria or viruses
56. Asthma
◦ Spastic condition of bronchiolar smooth muscle,
causing extreme difficulty in breathing
◦ Cause
◦ Usual cause is hypersensitivity of bronchioles to
foreign substances in air
◦ Mechanism
◦ Allergic person has tendency to form large
amount of IgE antibodies which attach to mast
cells
◦ On exposure to antigen IgE antibodies react with
it & mast cell granules rupture, releasing
substances
◦ These substances cause bronchospasm
