Respiratory Respiratory system - Physiology.ppt

Respiratory system - Physiology

1. THE RESPIRATORY
SYSTEM
Physiology II
Oct 8, 2025

2. Respiratory SystemRespiratory System –
Functions
Basic functions of the respiratory system are:Basic functions of the respiratory system are:
1. Primarily provides oxygen for tissue
respiration and removes carbon dioxide, a bi-
product of tissue respiration.
2. Secondary functions:
 Enables sound production or vocalization as
expired air passes over the vocal chords
 Enables protective and reflexive non-
breathing air movements such as coughing
and sneezing, to keep the air passages clear
 Control of Acid-Base balance
Oct 8, 2025

3. Anatomical &Physiological Classification of Respiratory
System
Oct 8, 2025
Anatomical-The respiratory system
divided into upper (nose, nasal cavity,
pharynx and larynx) & lower tracts
(trachea, bronchi, bronchioles,
alveolar ducts and alveolar sacs)
Physiological – divided into
conduction and respiratory portions

4. Oct 8, 2025
General functions of the conducting zone
Conduction and
conditioning/modification of air
(warming (37 °C), humidification (100%)
and filtration of air. It occurs in the nasal
cavity, trachea and bronchi & terminal
broncioles (particles larger than 2 mm).
Bears a specialized mucus ciliated
pseudostratified columnar epithelium
which is highly vascularized and rich in
goblet cells, lysozymes and antibodies.
Nostrils: Exterior openings with frank hairs and begins air
modification.
Nasal cavity: Well endowed to modify air, on addition to the
specialized epithelium, it has conchae/nasal turbinates that increase
air resistance and turbulence to increase air distribution within the
cavity and conditioning.

5. Air
Conducting
Zone
Oct 8, 2025
From Textbook of Work Physiology by
Astrand, Rodahl, Dahl & Stromme
Anatomically, there are twenty three (23)
generations. The trachea being the Zeroth
generation. The first 16 generations form
conducting zone of the airways - Bronchi
(primary-1, secondary and tertiary (2-3),
terminal bronchioles (4-16), respiratory
bronchioles (17-19), alveolar ducts (20-22) &
alveolar - 23
The first 3 generations + trachea bear cartilage
(U shaped in trachea but in bronchi turn into
small plates and disappears in bronchioles. The
bronchioles merely suspended by elastic tissues
in the lung parenchyma.

6. Cross sectional area –
increases down tracheo-
bronchial tree: 2.5 cm2
(trachea) & 10,000 cm2
(alveoli), number of branching
increases and decreased
diameter subsequently
increasing resistance and thus
decreases velocity of airflow;
all for the purpose of effective
gaseous exchange
Goblet cells decrease down
the tracheo-bronchiole tree.
As the cartilage decreases, the
amount of smooth muscles
increase.
Epithelium changes to simple
cuboidal and finally simple
squamous epithelium.
Air Conducting Zone

7. Oct 8, 2025
The remaining 7 generation form
the transitional & respiratory
zone (17-23). Gas exchange takes
place in this zone.
The functional respiratory unit is
an acinus.
Acinus is an aggregation of all
airways arising from a single
terminal bronchiole along with
associated blood vessels and
lymphatic vessels, respiratory
bronchioles, alveolar ducts and
alveolar sacs.
Respiratory Membrane & types of alveolar cells
Type I alveolar cells: Very thin
(simple squamous), allowing gas
exchange. Type II alveolar cells:
Thicker (cuboidal) - surfactant
secretion and
replenish type I. Alveolar macrophages

8. Surfactant and its Roles
Oct 8, 2025
Surfactant is a complex mixture of
phospholipids: 40%
Dipalmitoylphosphatidylcholine (DPPC),
26% of unsaturated lecithin, 0.9% of
Cholesterol, and 27% of apoproteins and
Calcium ions.
It has detergent like properties with
surface active phospholipids to reduces
surface tension and does not dissolve
uniformly in the water lining the alveolar
surface because it has a hydrophilic and a
hydrophobic portion.

9. Oct 8, 2025
Properties of the respiratory membrane
Alveoli (300 millions with a total surface area of 75 m2 to 100
m2 and very thin.
It measures between 0.1-
1.5micromiters thick) with the
following layers:
Alveolar fluid and surfactant
Single squamous layer of
alveoli
Single endothelial layer of
capillary
Fused basement membrane
between endothelial and
alveolar layers
Interstitial fluid

10. Oct 8, 2025
The Pleurae, Pleural Cavity & PressurePleurae: Double-layered
membrane, the parietal pleura
& the visceral pleura. Pleurae
epithelial cells secrete serous
fluid with a high turn over rate.
Drained by the lymphatic
vessels.
Pleural cavity: space between
the pleurae (has sub-
atmospheric pressure, the
intrapleural pressure - PIP).
Roles of the pleurae:
Couple lungs to the chest
wall, because of the negative
intrapleural pressure (PIP).
Reduce friction during
breathing movements due to
serous fluid secretion.

11. Lung perfusion - the process by which
blood is supplied to the lungs and includes
systemic circulation & pulmonary
circulation.
Systemic: delivers oxygen and nutrients
to trachea, bronchi and terminal
bronchioles by bronchial arteries and
bronchial veins drain, partly into the
azygus and hemi-azygus vein to inferior
venacava. ½ of the bronchial veins
anastomose with pulmonary veins adding
deoxygenated blood and thus reducing
slightly the oxygen tension of blood
(physiologic shunt).
The lungs comprise of 2 tree like structures vascular tree made up of
Arteries and veins, connected by capillaries
The pulmonary artery form a series of branching tubes
Flow the tracheal-bronchial plan leading to the pulmonary capillaries and back to
the pulmonary veins
About 300million alveoli : 280 billion capillaries (nearly 1000 capillaries/alveolus)
Total surface area of approx. 75-100m2 expressed by both lungs

12. High-flow, receive the entire volume of right ventricle cardiac output (5 L/min) and
low-pressure system with an average pressure = 25/8 mm Hg compared to 120/80
mm Hg systemic blood pressure & mean pulmonary arterial pressure, 15mmHg vs.
100mmHg in systemic circulation and pulse pressure, 17mmHg Vs. 40 mmHg in
systemic circulation.
These prevent the consequences of starlings forces and thus low net hydrostatic
pressure, yielding low fluid flow into pulmonary interstitial space (0.5L/day).
Reasons for the above properties:
The pulmonary arteries are much more
compliant (distensible, easier to stretch-thinner
walls.
Dense arterioles , capillary network and
vessels are shorter & wider
Thinner wall of the right ventricle doesn't
have to pump as hard to overcome peripheral
resistance.
Properties of pulmonary System

13. Lung volume: Lung inflation, increases
perfusion initially up to FRC from RV,
expands extra-alveolar vessels via radial
traction due to intrapleural pressure effect
but later decreases, from FRC-TLC,
collapses alveolar vessels via stretch of
alveolar wall
Alveolar vessels [pulmonary capillaries]
– alveolar pressure compression
Extra-alveolar vessels [pulmonary
arteries, arterioles, venules & veins]
Effect of lung volume& Exercise on perfusion
At rest some capillaries are: Open &
conducting or open not conducting or closed
and not conducting.
Exercise associated with increased BP and the
vascular system responds by distension &
recruitment thus - decreasing resistance and
increasing flow.

14. Oct 8, 2025
It is a collective term for the following processes:
Pulmonary Ventilation: Movement of air into the lungs
(inspiration) & Movement of air out of the lungs (expiration)
External Respiration: Movement of oxygen from the lungs to the
blood & movement of carbon dioxide from the blood to the lungs
Transport of Respiratory Gases: Transport of oxygen from the
lungs to the tissues & Transport of carbon dioxide from the tissues to
the lungs
Internal Respiration: Movement of oxygen from blood to the
tissue cells & associated energy metabolism and Movement of
carbon dioxide from tissue cells to blood
Regulation of respiratory process: Ventilation, external
respiration, transport of gases and internal respiration.
Respiration Process

15. Respiratory Pressures
(Transpulmonary pressure)
Atmospheric pressure is the weight of the
column of air above you (body), relatively
constant (760 mmHg or 0 cmH
2
0) at sea
level, pressure in the lungs must be higher or
lower than atmospheric pressure for air flow
to be created.
Intra-alveolar pressure (PA), pressure
inside the alveoli, where gas is exchanged.
It falls (to -1cmH
2
0) and rises (to +1cmH
2
0)
during inspiration and expiration
respectively. It always equalizes with
atmospheric pressure (0 cmH
2
0) at end
inspiration and expiration.
Intra-pleural pressure (IPP), pressure within the pleural space. It is
always less than intra-alveolar and atmospheric pressures (at rest, -3 to
-5 cmH
2
0 and -6 to -8cmH
2
0 at end inspiration.
Trans-pulmonary pressure (TPP):
The difference between the IPP and PA at
end inspiration (+6 to+8 cmH
2
0 ) and
expiration (+3 to +5 cmH
2
0 )
respectively. It is equal and opposite to
PIP, it is a lung recoil force.

16. Ventilation: Inspiration
T
Begins with nervous stimulation through,
respiratory nerves ( intercostal nerves, T1-T12)
innervate intercostal muscles of inspiration and
phrenic nerve innervate diaphragmatic muscles
At rest: External intercostal muscles, ribcage
stiffen to be able to withstand –ve IPP- 2nd to 10th
rib ( bucket handle effect, rotation of ribs upwards
and outwards increasing the transverse diameter.
Upper ribs ( water pump effect, rotate the sternum
upwards and outwards (chest’s antero-posterior
diameter increase, 25% of total change thoracic
vol. change).
Contraction of the diaphragm, moves it downwards (approx. 1cm at rest) and
straightens it out and increase the vertical diameter (75% total thoracic vol.
Change). IPP at beginning of inspiration is more negative (-8cmH20), couples
lungs to the outward recoiling thoracic wall, PA = -1cmH20 (decreased) less
PATM = 0cmHg, air flow begins till end inspiration and lung volume increased
to tidal volume- end inspiration: PA (0cmH20)= PATM (0cmH20) and TPP =
+8cm H20

17. Ventilation: Expiration
It is a passive process, no
contraction of muscles
Respiratory muscles relaxed
IPP = Changes from -8 to -
5cmH20
PA = 0cmHg (at end
inspiration).
Lung recoil force = + 8cmH20
(higher than IPP)
Pull the lung till +5cmH20 thus, PA = + 1 cmH20 higher than
atmospheric pressure (0 cmH20)
Air flows out until, PA (+1cmH20) = PATM (0cmHg) to attain a
stable state of equilibrium hence lung elastic recoil (+5cmH20) =
IPP(-5 cmH20 )

18. Elastic Properties of the lung
Demonstrated by lung Pressure Volume
Curve
Non linear, stiffer at high volume
Compliance = slope volume/pressure
Behaviors depends on structural
proteins (collagen, elastin) &
surfactant
Pressure causing different volumes of lung are different in
inspiration & expiration
called hysteresis i.e need higher pressure for a given volume in
inspiration vs. expiration:
lungs do not expand in linear fashion with ↓ing IPP: see a
sigmoid relationship
lung volume at any pressure on deflation (expiration) is larger
than during inflation
lung without expanding pressure (ie IPP=0) also has some
volume due to:
 air trapping in small airways
 because IPP = 0 so no forces acting to keep them open
 lung volume at which this small airway closure 1st occurs = closing capacity (RV+CV), this
airway closing occurs at higher volumes with ↑age and disease

19. Hysteresis
= effect lags behind the cause, in the lung
Need for higher expanding pressures for a
given lung volume during inspiration
compared to expiration (aka lung stiffer)
during inspiration
complex reasons:
elastic hysteresis: common to all elastic
bodies when stretched, elastic recoil on
shortening is always less than pressure
needed to stretch , manifestation of
energy loss
redistribution of air between different
alveoli
changes in surfactant activity with
changes in lung volume
changes in pulmonary blood volume

20. Cause of Regional Differences in Ventilation
Ventilation is not uniform in all lung
regions.
At higher IPP’s (i.e. less –ve, -2.5cmH20)
(base of the lung): lung relatively
compressed – less expanding pressure
BUT steep part of curve any ↓in
∴⇒
IPP big ↑volume, = better ventilation,
⇒
as ventilation = change in volume/unit
resting volume
At lower IPPs (i.e. more –ve, -10cmH20)
(apex of the lung): lung already
relatively expanded, increase in
ventilation with lowering IPPs will be
relatively less and poor ventilation

21. If IPP in base of lung becomes more +ve,
+3.5cmH20 (above atmospheric, 0cmH20).
The base of the lung being more compressed,
not expanded

∴
ventilation not possible until intrapleural
pressure falls below atmospheric, this
contrast upper lung now on steep part of
curve – good ventilation; apex good
ventilation, base very poor
•
∴
regional changes in ventilation depends on
lung volume:
normal volumes: base>apex
Abnormally low lung volumes: apex>base
Airway closure: the base does not lose all of gas, respiratory bronchioles close first
peripheral gas trapping, this airway closing occurs only at very low volumes in
⇒
young normal lungs & in elderly may occur at higher volumes ± at functional
residual capacity due to loss of elastic recoil in lung higher (less –ve) intrapleural
⇒
pressure bottom of curve above atmospheric pressure
⇒
Low volume; residual volume
(after forced expiration)
Cause of Regional Differences in Ventilation

22. Compliance
It is the change in lung tidal volume per unit
change in intrapleural pressure

23. Independent factors influencing compliance:
Lung volume: compliance is directly proportional to lung volume.
Posture: Lung volume, and thus compliance, changes with posture, erect = larger c/f
supine !
Pulmonary blood volume: ↑ pulmonary blood volume increases the “stiffness” of the
lung by engorgement
Age: Strangely, no correlation has been found b/w age and compliance, even after
allowing for changes in lung volume. lung elasticity = mainly determined by surface
∴
tension and not elastic tissue
Obesity
skin conditions especially scarring from burns
Restriction of chest expansion; this reduces both lung volume and lung compliance
(normal lung compliance can be restored by taking a single deep breath)
Recent ventilatory history: - period of hypoventilation without periodic deep breaths →
↓ in compliance. Normal compliance can usually be restored by 1 or more deep breaths.
(E.g. recruitment maneuvers with IPPV in ICU). Especially true for diseased lungs, little
evidence for use of “sighs” in ventilated normal lungs (e.g. during anesthesia)
Bronchial smooth muscle tone; Bronchoconstriction reduces dynamic compliance but
unlikely static compliance.
Disease: ↓ with oedema, pneumonia, lung fibrosis, ribs and state of ossification of costal
cartilages and ↑ with emphysema, asthma attack (↑ed volumes)

24. Elastic Properties of Chest Wall

25. Compliance of the Respiratory System
•Elastic properties of both lung & chest wall determine their combined
volume
•Compliance of entire respiratory system depends on combined
pulmonary compliance and thoracic wall compliance
•General Principle
•Lungs and chest wall compliance operate in series and add reciprocally:
1
C
1
C
1
C
Total Chestwall Lung
 
Thoracic cage compliance: Lung = 200ml/cmH2O and compliance
of thoracic cage is the same = 200ml/cmH2O. Instead of
compliance, can look at its reciprocal i.e. elastance. Elastance total
= elastance lung + elastance thoracic cage

26. Resistance to air flow
Air resistance is the pressure required to produce a flow of gas of 1 liter per
second through the air ways per minute.
Most air resistance is from medium sized bronchi (7th generation), smallest
narrow airways-reason being so many small airways ↑↑combined surface
⇒
area
Chief Site of Airway resistance
In adults:
nose 62%
URT 34% and
LRT 4%
Neonates:
Nose 28%
URT 46% and
LRT 26%
Note: Neonates are preferential nosal breathers

27. Pulmonary ventilation exchanges gases
between the ambient air and the alveoli of
the lungs (external respiration).
Ventilation, mechanical in nature, depends
on a difference between the atmospheric air
pressure and the pressure in the alveoli.
Gases flow from areas of higher pressure to
areas of lower pressure.
For inspiration, the atmospheric pressure is
greater than the alveolar pressure. The
reverse is true for expiration.
Minute Volume (VE): The volume of air inspired or expired per minute is known as VE .
Otherwise called total ventilation. It is the product of an average breathing frequency (f) of
12-15 breaths min −1 (also referred to as respiratory rate) and an average VT of 500 mL
⋅ ⋅
breath −1
At rest, VE averages about 6000 mL min −1(12 breaths min −1× 500 mL breath −1 ) or 6
⋅ ⋅ ⋅
L min −1 with a range between 5 and 8 L min −1 . With exercise, VE increased as a
⋅ ⋅
direct function of the oxygen needed at the cell level and the carbon dioxide produced by the
muscles. Either an increase in (f) or V T (depth) or both will increase total ventilation (VE)
V
E
= ( V
T
* f)
Pulmonary Ventilation

28. Oct 8, 2025
This is a portion of the minute
ventilation (Total ventilation) that fails
to reach areas of lungs involved in gas
exchange (respiratory zone).
Given the anatomical design of the
lungs, a small portion of the V
T
remains in the dead space (V
D). This
means that not all of the effort takes
part in the exchange of oxygen for
carbon dioxide at the alveolar–
capillary membrane.
That part of the VT that does not reach
the alveoli remains in the conducting
airways collectively termed the
anatomical dead space (nose, mouth,
trachea, bronchi, and terminal
bronchioles).
It was estimated to be equal to 150mls breath −1 for a subject who weighs 70kg, therefore,
the volume of air that does not participate in gas exchange dead space volume (VD ), at rest
given (f= 12-15) in adults, VD = * f (150*12) = 1,800mls.min −1 or 1.8 L min −1 (dead
⋅
space ventilation. Note that this volume in the anatomical dead space approximates body
weight in Kgs.
Anatomical Dead Space

29. Oct 8, 2025
Volume of fresh gas reaches the alveoli per
minute. It is calculated by subtracting the
anatomical dead space from VT , which is
then multiplied by (f)
VA = (VT – VD) * f
VA = (500 – 150) * 12
VA = 4200 ml/min
It determines the concentration of O2 and
CO2 in the alveoli
Alveolar ventilation is the most important
variable in gas exchange.
Alveolar Ventilation

30. Oct 8, 2025 Ventilation 30
Due to regional differences in
perfusion (diversion of blood to better
ventilated alveoli), Such alveoli do not
participate in gas exchange and they
constitute alveolar dead space
(functional dead space).
Total (physiologic) dead space include
anatomical dead space and
physiologic alveolar dead space.
In people with lung diseases, some
alveoli do not get blood supply and
thus pathological alveolar dead space
Alveolar (functional) Dead Space
Hypoventilation: inappropriately depressed level of alveolar
ventilation. It raises alveolar partial pressure of carbondioxide,
thus respiratory acidosis.
Hyperventilation: inappropriately elevated level of alveolar
ventilation. It lowers alveolar partial pressure of carbondioxide
resulting respiratory alkalosis.

31. Oct 8, 2025 Ventilation 31
Ventilation – Perfusion Ratio
Alveoli
Pulmonary capillary
Q
V
A

Defines a relationship between blood supply and
air flow in the lungs. Supposedly, blood & air flow
should be matched for diffusion of oxygen and
carbon dioxide to be adequate and most efficient.
Ventilation is symbolized as V, and perfusion is
symbolized as Q. Thus the ventilation perfusion
ratio is expressed as V/Q
In the lung with normal ventilation &
blood flow, some areas are well
ventilated but poorly perfused others
are well perfused but poorly ventilated
In either of these situation, gas
exchange at the respiratory membrane
would be impaired

32. Oct 8, 2025 Ventilation 32
Ventilation – Perfusion Ratio
Alveoli
Pulmonary capillary
Q (5L)
V
A

(4.2L)
For the entire lung
V
A
= 4.2 liters / min (RR=12
breaths/min)
Cardiac output, flow (Q) = 5 liters/
min
Thus the V
A/Q = 4.2/5 = 0.84 (This is
the normal ratio, If an alveolus is well
ventilated & well perfused
There will be normal gas exchange,
alveolar gas equilibrates with the
capillary blood partial pressures of O
2
& CO
2

33. Ventilation/perfusion ratio (V/Q)
October 8, 2025
Respiratory Physiology
By Dr. Francis Muzaale 33
Both Ventilation & Perfusion
increase slowly from top to
bottom of the lung
Blood flow increases more
rapidly than ventilation
V/Q ratio subsequently
different as you move from
one lung segment to the other
There is a steeper decline in
blood flow than ventilation
leading to V/Q ratios of about
0.8 at the bottom and around
3.3 at the top of the lungs.
Desirable V/Q =1, only at
rib number 3 region.

34. Level
of RA
Zone 1
V
A/Q >
0.8
Zone 2
V
A
/Q =
0.8
Zone 3
V
A/Q <
0.8
Upright individual, upper part is less well ventilated
than the lower part &is also poorly perfused
(7%CO), V
A
/Q > 0.8 (x3.3 more than the desired
ideal). No adequate blood flow to carry out gas
exchange; PAO
2
= rises, PACO
2
= falls and thus
respiratory alkalosis.
Conversely, still in an upright individual,
lower part is well ventilated, but it is also
very well perfused (13%CO) however,
perfusion is slightly better than ventilation;
V
A
/Q < 0.8 (x0.8 less than the desired), no
adequate ventilation to carry out gas
exchange, PAO
2
= falls, PACO
2
= rises
(Respiratory acidosis)
Gravity compressional
Forces, affect V & Q.
Ventilation – Perfusion Ratios in Lung
Dependant lung or part of the lung is one that lies
more in the gravitational field and gravitational
effects on ventilation and perfusion are expressed
more as opposed to non- dependant lung or part of
the lung

35. Oct 8, 2025 Ventilation 35
SHUNT
V
A
Q
P
VO2
= 40
P
VCO2
= 46
P
AO2
= 40
P
ACO2
= 46
V
A / Q = 0
P
aO2
= 40
P
aO2
= 46
Under normal circumstance, there are a
poorly ventilated alveoli, V
A is low
while Q is normal. The V
A/Q < 0.8 and
poorly aerated blood leaves pulmonary
capillary (shunted blood), this is
physiologic shunt. there is a fall in P
aO2
and only slight elevation of P
aCO2
,CO2
is eliminated in better ventilated alveoli.
If an alveolus is not ventilated but is well perfused. The V
A/Q = 0, there is
no gas exchange and the alveolar gas equal (=) the venous blood partial
pressures of O
2 & CO
2 , this called Shunt.
RECALL, CAUSE OF
REGIONAL VENTILATION

36. Oct 8, 2025 Ventilation 36
ALVEOLAR DEAD SPACE
V
A
Q
P
VO2
= 40
P
VCO2
= 46
P
AO2
= 149
P
ACO2
= 0
V
A / Q = ∞
If an alveolus is well ventilated but not perfused, V
A/Q = ∞ . There is no gas
exchange, this is alveolar dead space. Alveolar gas equals (=) atmospheric
air partial pressures of O
2 & CO
2
Under normal circumstances, the V
A is
normal but blood flow (Q) is decreased.
The V
A
/Q > 0.8, Some of the alveolar
ventilation (V
A) is wasted (No blood
flow to carry out gas exchange),this is
physiologic dead space
RECALL, CAUSE OF
REGIONAL PERFUSION

37. Physiological alleviation of alveolar Dead space
& Shunt
Oct 8, 2025 Ventilation 37
Alleviation of effects of alveolar dead space & Shunt
Level of the lungs
Hypoxic vasoconstriction, re-directing blood flow to well ventilated
alveoli- activated by reduced oxygen tension in lungs, increased H+ and
partial pressure of carbondioxide.
Regulation of local ventilation, bronchiolar constriction to poorly perfused
alveoli.
Decreased surfactant secretion, local reduction in compliance of poorly
ventilated.
Level of entire respiratory system: Increased ventilation
Compensatory responses to alveolar dead space and shunt help
protect body from consequences of V/Q mismatches. However,
bronchoconstriction and reduction in surfactant production
work well when a small amount of tissue is affected with still
ample amount of tissue available to which air can be redirected

38. October 8, 2025
Alveolar – blood gas Exchange
Fick’s law of diffusion
Determines the amount of gas that moves
across the respiratory membrane
Directly proportional to:
Surface area (A) of the tissue
Diffusion constant (D) of the gas
Pressure gradient of the gas
inversely proportional to thickness
(T) of respiratory membrane.
Blood travels for 0.75 sec through
pulmonary capillary, Oxygen
diffusion takes ~0.25s

39. Perfusion and Diffusion Limited
Perfusion limited
If a gas taken up by blood depends on
the amount of blood available e.g.
N2O– if the partial pressure reaches
equilibrium before the end of capillary
flow and stop diffusing then the agent is
perfusion limited because it has
maximally diffused.
Diffusion limited
If a gas taken up by blood depends on
the blood-gas barrier and not the
amount of blood available e.g. CO. If a
gas is still diffusing by end of a
capillary flow then it is diffusion
limited.
October 8, 2025
Oxygen under normal
healthy conditions is
perfusion limited, but in
pathological conditions
involving thickening of the
respiratory membrane,
diffusion limited as well

40. Diffusion limited Oxygen
October 8, 2025
Oxygen may become
diffusion limited in the
following circumstances:
Alveolar-capillary barrier
disease; decreases the rate of
diffusion, decreased surface
area and increased thickness
 High cardiac output;
decreases pulmonary transit
time.
 Altitude, decreases PAO
2.

41. Facts:
1 gm of Hb combine with 1.34 ml O
2 & 1mmHg capillary pressure
difference dissolves = 0.003mls of O2(solubility of O2 in plasma)
Oxygen Flux-Total amount
of O
2
transported by blood
per minute
Body Oxygen consumption Rate :
CaO2-CvO2 = 5Volume% or 5mls/100mls blood
Transport of O2: Two main means - dissolved in plasma (1.5% of
total transported oxygen) & bound to hemoglobin (98.5% of the
transported oxygen)

42. October 8, 2025
The extent to which Hb combine with O
2
increase very rapidly from 10 to 60 mm Hg
At P
O2
60 mm Hg 90% of Hb is combined with O
2
above P
O2
60 mm Hg
Further increase in P
O2 produces only a small increase in HbO
2 .
Flat portion between P
O2
70 to 100 mm Hg.
Normal arterial blood 98% saturated Hb (19.4 ml O
2
/ 100 ml blood). At the tissue level,
P
O2
is 40 mm Hg, Hb sat is 75%. Blood has 15 ml O
2
/100 ml blood.
O
2-Hb Dissociation curve

43. October 8, 2025
P50 is a measure of Hb
affinity for oxygen
Effect of pH on Hb-O2 Dissociation Curve

44. October 8, 2025
Factors influencing O2-Hb association Curve
Co
2 combines with the  - amino
groups of Hb, structural
configuration takes effect ( from the
R-form, oxygen loving form to T-
oxygen not so loving form) the Hb-
O2 bond weakens & off-loading of
O2 (right shift)
Increased H+ ions temperature and
2,3 DPG (binds to  chain of deoxy-
Hb
 have similar effects.
 Conversely, when pH is increased &
lowering of H+, 2,3 DPG and CO2
the structural change is from T to R,
oxygen loving, increasing affinity for
O2 thus loading Hb with O2 (left
shift)

45. October 8, 2025

46. October 8, 2025
At the placenta, fetal Hb must load at a
PO2 at which maternal Hb is
unloading ,dissociation curve is to the
left of maternal Hb’s curve.

47. Hypoxia
October 8, 2025
Symptoms may vary from individual to individual and severity of the
cause but early signs of hypoxia are anxiety, confusion, restlessness,
headache, shortness of breath, fast heartbeat, coughing, wheezing,
and chronic state; bluish color in skin, fingernails, and lips, clubbing
of fingers, systemic edema, excessive fatigue and acute forms;
stupor, coma or death
This a condition where there is reduced oxygen content in body fluids and
tissues or failure of cells to utilize available oxygen.
Hypoxia is actually divided into four types; hypoxic hypoxia, anemic hypoxia,
stagnant /Ischemic hypoxia, and histotoxic hypoxia.
Hypoxia can lead to many serious, sometimes life-threatening complications.
Oxygen therapy is a treatment that delivers oxygen gas for you to breathe. You
can receive oxygen therapy from tubes resting in your nose, a face mask, or a
tube placed in your trachea, or windpipe. This treatment increases the amount
of oxygen your lungs receive and deliver to your blood. However, the treatment
as it benefits fully particular types of hypoxia, some type of hypoxia benefit
slightly or not at all !!

48. October 8, 2025
Carbon dioxide is an exception gas limited by ventilation, rather than diffusion or
perfusion. This is because CO
2 is constantly being produced by the body, and needs
to be removed - it therefore moves in the opposite direction to the other gases. There
is a large amount of carbon dioxide in venous blood, present in various forms:
Dissolved in plasma (CO
2 is 20x more soluble in blood than oxygen)
Bicarbonate ions (part of the CO
2 and pH buffer system)
Carbamino compounds (largely bound to Hb for carriage to the alveolus)
This means that although CO
2
readily diffuses into the alveolus, the partial pressure
in the blood does not change because it is constantly being replenished both from
the above stores, and ongoing production by cellular metabolism.
If equilibrium is reached across the alveolar-capillary membrane, CO
2
transfer
will stop regardless of speed of diffusion or ongoing perfusion.
Therefore, the only way to ensure ongoing removal of CO
2
from the blood is to clear
it from the alveolus i.e. by maintaining alveolar ventilation.
CO2 is transported in three forms
Physically dissolved in plasma (7%)
As bicarbonate ions in plasma (70%)
As carbamino compounds (23%)
Carbondioxide Transport

49. Transport of CO2
October 8, 2025
Physically dissolved
depend on the partial
pressure & solubility
coefficient
Formation of carbamino
compounds amino groups
have ability to combine with
CO
2
, to form carbamino
compounds: R-N(H
2) + CO
2
R-NH-COO
⇌
-
+ H
+
In plasma there is no carbonic
anhydrase, equilibrium is far to
the left & accumulation of H
2
CO
3
stops the reaction but H
+
are
buffered by plasma buffers

50. Lung volumes & Capacities
•Differentiate between the
above two terms!!!
•Static volumes of the lung
are measured with a
spirometer
•Subject sits and breathes
into and out of the
spirometer, displacing a bell.
•The volume displaced is
recorded on calibrated paper

51. Tidal volume (VT).
•Volume of air taken in
and out during normal,
quiet breathing.
•First, the subject is
asked to breathe
quietly.
•Normal tidal volume
is approximately
500 mL
•volume of air that
fills the alveoli
plus
•volume of air that
fills the airways.

52. Inspiratory reserve volume & expiratory
reserve volume
•Additional volume
inspired above normal
tidal volume,
inspiratory reserve
volume (3000 mL.s)
•Additional volume
expired below normal
tidal volume, expiratory
reserve volume, (2000
mL.s)
•Subject is asked to take
a maximal inspiration&
then a maximal
expiration.
•Additional lung volumes
are revealed.

53. Residual Volume
•Residual volume
•Volume of gas
remaining in the
lungs after a
maximal forced
expiration (1200
mLs)
•Cannot be
measured by a
spirometer
(Why?)

54. Inspiratory & Functional Residual Capacity
•Inspiratory capacity
(IC): Maximal volume
of air inhaled after a
normal expiration
(TV+IRV = 3.6L)
•Functional Residual
Capacity (FRC):
•The volume of gas
that remains in the
lung at the end of a
passive expiration.
•(ERV+RV = 2-2.5 L)
•It is 40 % of the
maximal lung volume

55. Total Lung Capacity & Vital capacity
•Total Lung Capacity
(TLC):
•The maximal lung
volume that can be
achieved voluntarily.
•(IRV+TV+RV+ERV =
5-6L)
•Vital capacity (VC):
•The volume of air
expired with
maximum effort after
maximum
inspiration.
•(IRV+ERV+TV=4.5L

56. October 8, 2025
The amount of CO2 combining with
blood depends upon the PCO2, the
relationship between PCO2 combined
with blood is a linear relationship.
As the blood passes through the lung, an
influx of oxygen causes a right shift of
carbondioxide dissociation curve while
the partial pressure of carbondioxide
drops from 45-46mmHg to about
40mmHg. This serves to release a
greater amount of CO2 into the alveolar
space.
Arterial blood has 48mls of CO2 per
100mls of blood (or 48 mls volume %)
and venous blood contains 52mls
Volume%. Each 100 mls of venous blood
release 4 mls volume % (52mls-48mls)
while passing through lungs.
Thus, CO2 eliminated per minute is
200ml (remember cardiac output =
5000mls/min).
Carbondioxide Blood Content

57. October 8, 2025
Breathing at rest occurs
due to repeated
contraction and relaxation
of inspiratory muscles.
The rate of breathing is
regulated by the brain
stem (Medulla and pons)
It monitors the level of
oxygen and carbon
dioxide in the blood and
triggers faster or slower
breathing as needed to
keep the levels within a
narrow range.
Regulation of Respiration

58. October 8, 2025
Neural Control of Respiration
Two neural control mechanisms
One responsible for voluntary control, located in
cerebral cortex and send impulses to respiratory muscles via
corticospinal tracts (CST)
The other one for automatic control, located in pons
(Apneustic, Pneumotaxic centers) and medulla oblongata
(DRG, VRG). Efferent (descending) output from this
system to respiratory muscles and located in spinal cord
close to CST

59. October 8, 2025
The DRG contains
inspiratory neurons
only.
Most of the neurons of
DRG are found in the
solitary nucleus (NTS),
while some are found in
the reticular substance
of the medulla.
Dorsal respiratory group (DRG)

60. October 8, 2025
The ventral respiratory group is made
up of both expiratory & inspiratory
neurons.
VRG is located anterior and lateral to
DRG (ventrolateral) portion of the
medulla.
Made up of the most rostral
interneurons of Botzinger complex
(central pattern generator important for
the generation of respiratory rhythm in
VRG), intermediate nucleus
retroambiguus (rostral and caudal),
most caudal, ambiguus.
Ventral respiratory group (VRG)
The neurons of VRG are active during forceful breathing and are
inactive in case of restful respirations. The apneustic center receives
inhibitory impulses from VRG.

61. October 8, 2025
It consists of pneumotaxic and apneustic
centers.
Both these centers are connected, and they
are also connected to the solitary nucleus.
Pneumotaxic center is present in the
upper part of the pons.
Sub parabrachial nucleus and medial
parabrachial nucleus are the nuclei of
this center.
The pneumotaxic center has all the
information that is needed for respiration,
and hence breathing would not be possible
if this center is harmed or damaged.
Pontine respiratory group
The apneustic center is located in the lower part of the pons.
Pneumotaxic center and pulmonary stretch receptors inhibit the
apneustic center.

62. October 8, 2025
The pneumotaxic regulates the pattern and rate of breathing. It limits
inspiration by providing an inspiratory off switch (IOS); limits action potential
bursting in the phrenic nerve, and regulates the amount of air taken inside for
each breath (damage, slow and deep breathing).
The apneustic center constantly stimulates the neurons of the medulla and
promotes inhalation. It sends a signal to DRG to delay the IOS. The intensity of
breathing is controlled by giving positive impulses DRG. Pneumotaxic center
and pulmonary stretch receptors inhibit the apneustic center ( damage,
respiration is shallow and irregular).
DRG exhibit self excitation sending out repetitively bursts of action potentials,
the basic rhythm of breathing is generated in the DRG. Various sensory input
coming from the pontine respiratory group, chemoreceptors or stretch receptors
(via vagus (X), and glossopharyngeal (IX) nerves) ends in the solitary nucleus
to modify the spontaneous basic rhythm of breathing. This is to provide for a
smooth and regular respiratory rhythm commensurate with the needs of the
body.
QUIET BREATHING (EUPNEA)

63. October 8, 2025
Restful breathing nerves serving
inspiration converge in ventral
horns
C
3,4,5
(phrenic nerve)
External segmental intercostal
motor neurons
With expiration, inspiratory
nerves cease firing and elastic
recoils of the chest wall and lung
help in expiration
QUIET BREATHING
Reciprocal activity occurs, motor neurons to expiratory muscles
inhibited when those to inspiratory muscles are activated & vice versa.
Expiratory neurons (E-neurons) during quiet breathing remain silent
and only become active when ventilation is increased.

64. October 8, 2025

65. October 8, 2025
Regulation of the Basic Rhythm of Breathing
•Pulmonary ventilation is regulated to meet
different levels of metabolic demands; supply
of O
2
and elimination of CO
2
•Achieved by feed back control of respiratory
center activity in response to chemical
composition of blood i.e; P
CO2, H
+
, and P
O2
•Primary chemoreceptors include;
•Central chemo-receptors
•Peripheral receptors

66. October 8, 2025
Chemosensitive neurons are
bilateral beneath the ventral
medulla
Sensitive to changes in P
CO2 &
H
+
Chemical Regulation: Central Chemoreceptors
H
+
is the direct stimulus,
but BBB has very poor
permeability to H
+
so,
changes in H
+
in blood no
immediate effect on
respiration.
CO
2 diffuse easily across
BBB, hydrated and
dissociates to H
+
& HCO
3
-
CSF is low in buffers and
thus, increase in CSF CO
2
causes chemoreceptors to
stimulate respiration and
vise versa.
Excessive elimination of
CO
2
depresses CO
2
in body
fluids and thus respiratory
alkalosis. ↓H
+
conc CSF
inhibit the resp. drive

67. October 8, 2025
Located in the carotid & aortic bodies
respond to lowered arterial O
2
tension, rise
in arterial CO
2
tension & increase in H
+

conc in arterial blood
Aortic bodies primarily monitor O
2

tension rather than O
2
content,  O
2
caused
by anaemia, methaemoglobin, CO
poisoning do not stimulate peripheral
chemoreceptors.
When P
O2
falls below 60–80 mm Hg,there
is an increase in rate of discharge of fibers
from the receptors to respiratory center
and thus↑ rate and depth of respiration,
alveolar ventilation and elimination of
CO
2
Chemical Regulation: Peripheral Chemoreceptors
Elevation of CO
2
tension also stimulate peripheral
chemoreceptors but most of effect of CO
2
is on the central
chemoreceptors.
↑in H
+
conc Stimulate peripheral chemoreceptors resulting
into increase in ventilation and increase in alveolar ventilation
↓CO
2
tension, pH returns towards normal and ventilatory drive
tends to reduce.

68. October 8, 2025
Other receptors
Nose & upper airway receptors; upper respiratory pathways contain
receptors that respond to mechanical, chemical stimuli and reflex initiated
is sneezing, coughing, and bronchoconstriction.
Irritant receptors; lie in large airways between airway epithelial cells
and stimulated by noxious gases, smoke, particulates in inhaled air. These
initiate reflex that stimulate coughing, bronchospasm, mucus secretion
and breath holding (apnoea).
J-receptors (Juxta-capillary); located in the pulmonary interstitium at
the level of pulmonary capillaries. Stimulated by the distension of
pulmonary capillaries caused by ventricular failure, emboli, or chemicals.
Initiate reflex that cause rapid, shallow breathing, tachypnea
Baroreceptors (carotid body), a rise in BP cause reflex hypoventilation
and a fall in BP cause reflex hyperventilation.

69. October 8, 2025
Pulmonary stretch receptors
The signals go via vagus nerve to the DRG and influence inspiratory neurons, cutting
of the vagus nerve results into characteristic deep and slow breathing. Pons act as
central relay station of vagal input.

70. October 8, 2025

71. October 8, 2025
Test Your Wit
1.Define the following terms; dyspnea, tachypnea,
hyperpnea, hypopnea and eupnoea.
2.Identify and explain the factors (physiological and
pathological) responsible for the conditions in (1.) above.
3.Define respiratory failure and identify factors responsible
for respiratory failure.
4.Explain the physiology of sleep apnea (central and
obstructive) and the clinical significance
5.Explain the effect of the following on the respiratory
rhythm; body temperature, mental alertness, sleep, alcohol,
sedative drugs and anesthetic drugs

72. Factors Determining Airway Resistance
lung volume
Bronchial smooth muscles
Viscosity & Density of
Inspired gas
Type of Flow
Dynamic Compression of
airways
Course Work 1: a) Explain fully how each of the 5 factors below
influence airway resistance
b) Explain why it is better to increase VE during exercise with an
increase in tidal volume rather than frequency of breathing

73. Test your Wit
1.Define cyanosis by types i.e.: central cyanosis and
peripheral cyanosis.
2.What are the likely causes of cyanosis
3.By what level of Hb reduction does an individual start
getting cyanotic
4.Define hypercapnia and explain the symptoms and signs
(pathophysiology) associated with hypercapnia
5.Define and give the causes, and symptoms associated with
hypocarpnia
6.Identifying the likely causes, how do “Blue bloaters”
compare with “Pink puffers”?