Anaesthesia

1. LUNG COMPLAINCE ,
RESISTANCE AND
WORK OF
BREATHING.
-Dr.AGALYA
II YEAR RESIDENT
DEPARTMENT OF
ANAESTEHSIA

2. MECHANICS OF
RESPIRATION
❖ Inspiration occurs when the Palv < Patm
and may be due to:
1) Negative pressure respiration
Lowering alveolar pressure below Patm.
2) Positive pressure respiration
Increasing Patm above Palv
❖ Expiration occurs when Palv >Patm

4. Normal Breathing
❖ Commences with active contraction of Inspiratory
muscles :
a.Enlarges the thorax.
b. Decreases intraalveolar and intrapleural pressure
c.enlarges alveoli, bronchioles ,bronchi.
d.lowers Palv< Patm.
❖ Air flows from mouth and nose to alveoli

5. ❖ Inspiratory muscles provide necessary force to
overcome :
a. Elastic recoil of the lungs and chest wall.
b.Frictional resistance

7. ELASTIC RESISTANCE TO
BREATHING
❖ The tendency of elastic lung tissue to recoil from the
chest wall results in Sub atmospheric intrapleural
pressure
❖ At FRC , the mean Intrapleural pressure : -4 to -5cm
h2o

8. COMPLIANCE

9. COMPLIANCE
❖ The ability of the lungs to expand is expressed as Lung
Compliance .
❖ C =🔺V /🔺 P

10. Elastic Recoil of the thoracic
cage
❖ Thoracic cage compliance is calculated as :
1/Ctot = 1/CL + 1/ Ccw.
❖ Normal values :
Total thoracic compliance Ctot = 0.1 L/cm H20
Compliance of lung CL = 0.2L/ cm H20
Chest wall compliance = 0.2L/ cm H20
❖ Lung compliance : static/Dynamic
❖ Thoracic cage compliance decreases in :
Kyphoscoliosis, Scleroderma, Muscle spasticity ,
Abdominal distension

11. STATIC COMPLIANCE
❖ Relationship between volume change of lung and the
transpulmonary pressure change , i.e. airway- Intrapleural
pressure change measured under static conditions
❖ Airflow is zero at the point of flow reversal during the normal
respiratory cycle
❖ Reflects elastic resistance of the lung and chest wall
❖ Cst = Vt /( Pplt -PEEP)
❖ Normal ~ 200ml/cm H2O (0.2L/cm H20)
❖ Value decreases as lung volume increases , due to
limitations of non-elastic components of lung/chest wall
system .

12. Measurement of static
compliance :
❖ Patient takes a breath from spirometer and holds it until
TPP difference becomes stable
❖ Repeated with different tidal volumes to produce a
pressure/ volume curve
❖ Can be done with the patient apnoeic using PPV
(Patients on Mechanical Ventilators)

13. ❖ FACTORS AFFECTING STATIC COMPLIANCE :
❖ 1. Lung volume
❖ 2. Pulmonary blood volume
❖ 3.Age
❖ 4. Restriction of chest expansion

14. HOW STATIC COMPLIANCE
WORKS
❖ 1) Healthy lungs : Application of pressure of 5cm H20
results in inflation of 1 litre of Air :
C = 1L/5cmH20 = 0.2 L/cmH20 : NORMAL
❖ 2)In Emphysema : Application of a pressure of 5cm
H20 results in an Inflation of 2Litres of Air :
C = 2L/5cm H20 = 0.4 L/cmH20 : INCREASED
❖ 3) In Pulmonary Fibrosis : Application of a pressure of
5cmH20 results in inflation of only 0.5 ltr of air
C = 0.5L/5cmH20 = 0.1L/cmH20 : DECREASED

15. DYNAMIC COMPLIANCE
❖ Dynamic compliance is defined as Change in lung
volume per unit change in pressure when there is
Airflow.
❖ Reflects the airway resistance + Elastic resistance
❖ C dyn = Tidal volume / PIP-PEEP
❖ In normal lungs at low and moderate frequencies ,
dynamic and static lung compliances are same

16. Measurement of Dynamic
compliance
❖ Taken from the slope of Transpulmonary pressure/
volume loops recorded during tidal ventilation
❖ Using a differential pressure transducer , from an
esophageal balloon to the airway
❖ Factors affecting Dynamic Compliance :
Decreased Cdyn seen with increased airway resistance.
Eg: Asthma , Chronic Bronchitis , Emphysema

17. Factors affecting Respiratory
Compliance

18. High compliance
❖ Volume change is large per unit pressure change
❖ In extreme high compliance situations there is incomplete
Exhalation due to lack of elastic recoil of the lungs
❖ Seen in conditions that increase FRC
❖ Emphysema is one such condition where there is
destruction of lung tissues , enlargement of terminal and
respiratory bronchioles leading to air trapping and
impairment in gaseous exchange

19. COMPLIANCE OF LUNGS
❖ The pressure volume loop
❖ Since compliance is determined by 🔺V/🔺P
, the P-V loop provides characteristics of
patients compliance.
❖ 2 curves according to different phases of
respiration :
Inspiratory compliance curve and
Expiratory compliance curve
❖ AREA IN THE LOOP: Total work of
breathing done Against Elastic and
Airway Resistances

22. ❖ When the
forward path
is different
from the
reverse path
, it’s referred
as
Hysteresis .

23. Lung Compliance and
Elastance
❖ Elastance is the reciprocal of compliance , that is the
pressure change that is required to elicit a unit volume
change . It’s measure of the resistance of a system to
expand
❖ Elastance = 1/compliance = Pressure change / Volume
change

24. RESISTANCE TO
BREATHING

25. RESISTANCE OF RESPIRATORY
SYSTEM
❖ Resistance is the Mechanical Impedence offered to
Respiration .It impedes Airflow into and out of the lung
❖ Definition : It is the pressure required to produce a flow of
1L/s into and out of the lungs
❖ It’s calculated as driving pressure divided by Resultant
gas flow
❖ R= 🔺P / F
❖ Unit is centimeters of water per liter per second
❖ Average Resistance is 1 to 3 cm H2O/L /sec

26. RESISTANCE TO BREATHING
A)Elastic Resistance -65%
B)Non Elastic Resistance -35%.
I) Airflow resistance ~80%.
II) Viscous resistance ~20%

27. Elastic Resistance
❖ The Elastance of the whole respiratory system depends
on the Elastance of the chest wall and that of the lungs
❖ Elastance in each of the lungs and the chest wall is
approximately 5cm H20 . Elastance of the respiratory
system is 10 cm H20

28. ❖ Variations in the Elastance of respiratory system are
mainly due to alterations of the Elastance of lungs
governed by two main factors :
❖ - Elastic recoil forces of lung tissue
-Forces exerted by Surface tension at Air-Alveolar
interface

29. Factors affecting Elastic
Resistance
❖ I) Elastic recoil
forces of lung tissue :
❖ 1.Elastin fibres forming the
pulmonary interstitium resist
stretching and exhibit property
of returning to its original length
when stretched .
❖ 2. Accounts for 1/4th to 1/3rd of
elastic resistance of the lungs

30. II) Forces Exerted by
surface tension at Air-
Alveolar Interface
-Responsible for remaining
2/3rd to 3/4th of Elastance of
lungs
-Alveoli have thin line of fluid
,which comes in contact with
air , the net surface tension
acts inward
LAPLACE’S LAW :
Pressure = 2* Surface tension
__________________
Radius

31. ❖ To prevent alveoli from collapsing a transmural pressure
should be acting across the alveolar wall.
❖ This pressure , for a single alveolus =
2* surface tension / Radius of alveolus (2T/r)
❖ RADIUS = PRESSURE TO COLLAPSE
❖ Smaller alveoli have greater tendency to collapse

32. SURFACTANT
❖ Surfactant is surface tension
reducing agent .
❖ Composed mainly of Di-
Palmitoyl Phosphatidyl
choline
❖ Secreted by Type II Alveolar
cells
❖ Reduction in ST leads to
Reduction in TPP Required
to keep the alveoli open
thereby work of breathing
also reduced

33. ❖ Loss of Alveolar walls results in
1) Loss of surface Area for diffusion
2) Loss of Alveolar Interdependance : Greater tendency
to collapse and local Atelectasis can occur

34. Non Elastic Resistance To
Breathing
❖ Composed of :
1) Airway resistance = 80%
2) Viscous resistance = 20%

35. AIRWAY RESISTANCE
❖ Airflow obstruction in the Airways
❖ Pressure required tp overcome the resistance to gas
flow through the Airways during Respiration ~ 0.5- 1.5
cmH20/L/Sec

36. TYPES OF AIRFLOW
PATTERNS:
❖ Laminar Flow
• Below critical flows, gas proceeds through a straight tube as a
series of concentric cylinders that slide over one another. Fully
developed flow has a parabolic profile with a velocity of zero at
the cylinder wall and a maximum velocity at the center of the
advancing “cone.”
• Peripheral cylinders tend to be stationary, and the central
cylinder moves fastest.The advancing conical front means that
some fresh gas reaches the end of the tube before the tube has
been completely filled with fresh gas.

38. ❖ A clinical implication of laminar flow in the airways is that
significant alveolar ventilation can occur even when the tidal
volume ( Vt) is less than anatomic dead space. This
phenomenon, noted by Rohrer in 1915, is important in high-
frequency ventilation.
❖ Hagen-Poiseuille Equation For Gas Flow In a Straight
Unbranched Tube
❖ π (Pb – Pa) r4 / 8nL = R
❖ where Pb= Atm. Pr., Pa= Alveolar Pressure, R= flow rate

39. ❖ Turbulent Flow
• High flow rates, particularly through branched or irregularly
shaped tubes, disrupt the orderly flow of laminar gas.
• Turbulent flow usually presents with a square front so fresh
gas will not reach the end of the tube until the amount of gas
entering the tube is almost equal to the volume of the tube.
Thus, turbulent flow effectively purges the contents of a tube

41. • conditions that will change laminar flow to turbulent
flow are
– 1) high gas flows,
– 2) sharp angles within the tube,
– 3) branching in the tube,
– 4) change in the tube's diameter.
• During turbulent flow, resistance increases in proportion
to the flow rate. Turbulent flow occurs when there is a
net forward flow, but there are many local eddy currents
(little circulations that occur).
• Turbulent flow of air is observed in the upper airways
where the radius is larger and the airflow is more rapid.

42. REYNOLDS NUMBER
• The Reynolds number is used as an index to determine whether flow
is laminar or turbulent. It is a unitless number that is defined as:
❖ Re = 2rvd/η,
❖ where r is radius, v is velocity, d is density, and η is viscosity.
❖ < 2000 - Laminar.
❖ > 4000 - Turbulent.
❖ 2000 – 4000 – Both

43. Contd.
❖ According to this equation, turbulent flow is likely if the tube
has a large radius, a high velocity, a high density, or a low
viscosity

44. Factors Affecting Airway
Resistance
❖ Poiseuille’s Law : Δ P = V/r4
❖ where P= Pressure required to maintain airflow V= Volume of
airflow
❖ r = Radius of airway
❖ Thus the airway resistance may be increased by any condition
where the caliber of the airway decreases. (radius)
❖ Viscosity and Density of the gas mixture
❖ Length, and lumen radius of artificial and patient’s
airways: Airway resistance and lumen radius are exponentially
related to the fourth power. Because of this relationship any small
amount of bronchospasm, secretion accumulation, in the
endotracheal tube, water in the ventilator tubing, or other
obstruction considerably increases airway resistance

45. Contd.
• Flow rate: The higher the flow, the greater the amount of
turbulence and consequent increase in the airway resistance.
Conversely, a slow flow rate minimizes turbulence and
airway resistance.
• Flow pattern: Laminar flow decreases airway resistance
whereas turbulent flow increases it.
• Lung Volume: In general, as lung volume increases,
resistance decreases. This is due to radial traction exerted on
the airways. When the volume of the lung increases, the
radius of the conducting airways increases and the result is
lower airway resistance.
• Bronchial Smooth Muscle Activity

46. 33
Airway Resistance
0 5
0.00
0.02
Resistance
10 15 20
Airway Generation
Terminal bronchioles
Segmental
bronchioles
Midsize airways are normally the source of major resistance
0.10
0.08
0.06
0.04

47. • Respiratory bronchioles have small individual radii. Yet
the parallel arrangement of these small airways results
in a large total cross sectional area creating little
resistance to airflow.
• In airway disease the smaller airways are the major
site of resistance to flow of air because of a reduction in
their luminal size.

48. Conditions increasing Airway
Resistance
TYPE CLINICAL CONDITION
COPD Emphysema
Chronic Bronchitis
Bronchiectasis
MECHANICAL OBSTRUCTION Post intubation
Obstruction by FB
Aspiration
Infection Laryngotracheobronchitis
Epiglottitis
Bronchiolitis
Miscellaneous Asthma
Bronchospasm

49. ❖ Effects of Increased Airways Resistance
1. Lung hyper-inflation → increased FRC and residual
volume
2. Dyspnoea
3. Decrease in respiratory rate
4. Mechanical Exhaustion of respiratory muscles (Inc.
WOB)
5. V/Q mismatch

50. Pulmonary Tissue Viscous
Resistance
• Mainly due to the movement of pleural layers between lobes,
and between the lungs and chest wall during inspiration &
expiration
• Accounts for < 20% of the total non-elastic resistance in
health
• Increased in pulmonary fibrosis, carcinomatosis, etc., but
rarely to significant or limiting values.
• Measurements of thoracic cage viscous resistance, rib cage &
abdominal contents,is difficult.

51. WORK OF
BREATHING

52. WORK OF BREATHING
❖ Definition: It is the work required by the respiratory muscles
to overcome the mechanical impedance to respiration. It is the
sum of work requires to overcome both elastic and airflow
resistance.
• There are two categories that the physical work of breathing
can be broken down into.
• One type is resistance work in which an increase in resistance
results in an increase in work.
• Compliance work is the other type of breathing work done. A
decrease in compliance of the lungs requires an increase in
work of them.

53. ❖ Airway Resistance & Work of Breathing
• As given in the equation Raw = ΔP/V (Raw = Airway
resistance
❖ ΔP = PIP-Pplat V= Flow )
• The pressure change ΔP, can be treated as the amount of work
imposed on the patient.
❖ Thus the work of breathing is directly proportional to the
airway resistance and an increase in the airway resistance
increases the work of breathing.
• If the work of breathing remains constant then an increase in
the airway resistance will decrease the flow. In the clinical
setting if the patient is unable to overcome the airway resistance
by increasing the work of beathing then hypoventilation may
result in decrease of the minute ventilation of the patient.

54. COMPLIANCE AND WORK
OF BREATHING
•Since compliance is inversely related to pressure change, a decrease in
compliance will result in increase in the work of breathing. In the
clinical setting, atelectasis is one of the most frequent causes of
increased work of breathing.
•If the change in pressure remains constant then the decrease in
compliance will cause a decrease in the tidal volume and minute
ventilation.
•Thus in low compliance situations such as ARDS the decrease in minute
ventilation is characterized by low tidal volume and high respiratory
rates

55. ❖ In summary, the work of breathing can be
increased by
– increased airway resistance,
– reduced lung compliance, or
– reduced thorax compliance

57. Expiration : Two shaded areas overlap
indicating it’s a PASSIVE PROCESS

58. WORK OF BREATHING AND
RESPIRATORY RATE

59. ❖ Work of Breathing during Normal Respiration
• During normal quite breathing, respiratory muscles work during
inspiration to expand the lungs, whereas expiration is a passive process.
• Normally lungs are highly compliant and airway resistance is low, so only
3% of total energy is used by the body during quite breathing.
❖ Clinical Application
❖ Work of breathing may be increased:
1. When pulmonary compliance is decreased.– more work is required to
expand the lung. eg Pulmonary Fibrosis
2. When airway resistance is increased: more work is required to overcome
the resistance. Eg. COPD.

60. ANAESTHETIC
IMPLICATIONS

61. RESPONSE TO INCREASED
RESISTANCE
• The reduction in FRC associated with General Anaesthesia
increases the Airway Resistance
• Increased Resistance Usually Compensated due to
Bronchodilating effects of Volatile Anesthetics

62. Contd.
• INCREASED AIRWAY RESISTANCE is usually due to
Pathological factors like :
i) Tongue fall
ii) Laryngospasm
iii) Bronchoconstriction
iv) Equipment problems

63. Contd.
• There is even greater ability to compensate for increase in
expiratory resistance up to 10 cmH2O there is no activation of
the expiratory muscles, awake or anaesthetised.
• The additional work is performed by the inspiratory muscles,
shifting the tidal loop further up the compliance curve,
allowing the increased elastic recoil to overcome the
increased resistance

64. EFFECT ON COMPLIANCE
• Compliance is significantly decreased
• The majority of the change occurs in the lung, there being little
alteration of chest wall compliance.
• Pressures ≥ 30 cmH2O inflate the lung to only 70% of the
preoperative total lung capacity. This reduction occurs early in
anaesthesia and is not progressive
• There is no general agreement on a direct effect of anaesthetics on
pulmonary surfactant. Some studies have shown a decreased activity
• Alternative explanations include :
– a. breathing at a reduced lung volume
– b. pulmonary collapse in the dependent regions
– c. the reduced compliance is a cause of the decreased FRC

66. EFFECT ON WORK OF
BREATHING
• An increase in respiratory muscle loading secondary to an
increase in physiologic and/or imposed WOB results in
increased force and duration of diaphragmatic contraction,
increased oxygen consumption and respiratory muscle
fatigue.
• Insertion of an oral airway during spontaneous mask breathing
reduces inspiratory WOB significantly from that without an
airway.

67. Contd.
• The addition of CPAP significantly reduces WOB, probably
because of “stenting” of the pharyngeal soft tissue, preventing
the tissue from being sucked together by negative
intraluminal pressure.
• ETT with a relatively smaller diameter increases flow
resistance and the resistive WOB although Vt is maintained
by associated increases in inspiratory time. LMA exerts much
less resistance.

68. PULMONARY
CIRCULATION
TRANSPORT OF
OXYGEN AND
CARBONDIOXIDE

69. Pulmonary circulation
❖ The lungs have two functionally distinct circulatory pathways.
❖ The pulmonary vessels convey deoxygenated blood to the
alveolar walls and drain oxygenated blood back to the left side of
the heart.
❖ The pulmonary vasculature is unique in that it accommodates a
blood flow that is almost equal to that of all the other organs in
the body.
❖ The bronchial vessels are derived from the systemic circulation,
provide oxygenated blood to lung tissues that do not have close
access to atmospheric oxygen, i.e. those of the bronchi and
larger bronchioles.

71. ❖ There are usually four pulmonary veins,
two from each lung. They originate from
capillary networks in the alveolar walls and
return oxygenated blood to the left atrium.
❖ The pulmonary veins open into the left
atrium and convey oxygenated blood for
systemic distribution by the left ventricle.

73. VENTILATION
PERFUSION
RELATIONSHIPS

74. VENTILATION
❖ Ventilation refers to the gross movement of air into
and out of the lungs.
❖ Ventilation consists of two components:
1. Alveolar ventilation: the movement of air into the
alveoli for the purpose of gas exchange
2. Dead space ventilation: the movement of air into the
conducting airways, which does not take part in gas
exchange.

75. Contd.
❖ Ventilation is measured as sum of all exhaled gas
volumes in one minute(MV)
❖ Minute Ventilation = RR Tidal volume
❖ Alveolar Ventilation = RR (Vt – Vd)
❖ Physiological Dead space = Anatomical dead space +
Alveolar Dead space

77. DISTRIBUTION OF
VENTILATION
❖ Alveolar ventilation is unevenly distributed regardless of
body positions
❖ Lower Dependant areas- Base ventilated better than
Upper Areas (Apex)
❖ Pleural pressure decreases by 1cm H2O (becomes less
negative ) per 3 cm decrease in lung height
❖ Apex : TPP is higher , Maximally inflated , Relatively
Non compliant and Little expanded during Inspiration
❖ Base : TPP is lower , More Compliant , Greater
Expansion during Inspiration

79. PERFUSION
❖ Total pulmonary blood volume varies between 500-
1000ml
❖ Large increase in blood volume are tolerated with little
change in pressure due to passive dilatation of blood
vessels
❖ A shift in posture from supine to erect decreases
pulmonary blood volume upto 27%

80. DISTRIBUTION OF
PERFUSION
❖ Regardless of body position , Pulmonary Blood flow is
not uniform
❖ Base : Greater blood flow
❖ Apex : Less blood flow
❖ Lungs divided into 4 zones based on interplay between
these pressures: PA- Alveolar pressure
Pa – pulmonatry Arterial Pressure
Pv – Pulmonary venous pressure

82. Pulmonary
Shunting
• PERFUSION WITHOUT VENTILATION.
• Pulmonary shunt is that portion of the cardiac
output that enters the left side of the heart without
coming in contact with an alveolus.
– “True” Shunt – No contact
• Anatomic shunts (Thebesian, Pleural, Bronchial)
• Cardiac anomalies
– “Shunt-Like” (Relative) Shunt
• Some ventilation, but not enough to allow for complete
equilibration between alveolar gas and perfusion.
• Shunts are refractory to oxygen therapy.

84. VENTILATION/ PERFUSION
RATIOS
❖ Normal Alveolar Ventilation : 4L/mt
❖ Normal pulmonary Capillary Perfusion : 5L/mt
❖ V/Q : 0.8
❖ Apex : Higher V/Q
Base : Lower V/Q

86. ❖ Respiration refers to the exchange of oxygen and carbon
dioxide across semi permeable membrane .
Respiration consists of two components
❖ External respiration: That occurring in the lungs
❖ Internal respiration: That occurring in the cell.
RESPIRATION

87. GAS EXCHANGE AND
TRANSPORT OF OXYGEN

88. Sequence Of Oxygen
Transport
1) Mass Transport from Environment to Alveolar SpacE
2) Diffusion from Alveolar Air to Blood in the Pulmonary
Circulation
3) Mass Trasport from pulmonary to Systemic Capillaries
4) Diffusion of Oxygen From Capillary blood to
Metabolizing Cells And within the cell to the site of
Consumption

89. 1) ENVIRONMENT TO
ALVEOLI
❖ ATMOSPHERIC OXYGEN TENSION (PiO2 )
Atmospheric air containing 21 % oxygen at a total atmospheric
pressure of 760 mm Hg at sea level has a pO2 of
approximately 160 mm Hg.
ALVEOLAR OXYGEN TENSION( PAO2)
❖ With every breath, the inspired gas is humidified at 37°C in
the upper airway. The inspired tension of oxygen (PIO2) is
therefore reduced by
❖ the added water vapor. Water vapor pressure is 47 mm Hg at
37°C. In humidified air, in the trachea the normal partial
pressure of O2 at sea level is 149.7 mm Hg:(760-47)0.21

90. ❖ PIO2 = PB * FiO2
❖ Since inspired air is humidified ,
PIO2 = (PB – PH20 )* FiO2
Substituting the values :
PIO2 = (760 – 47) * 0.21 = 149.7mmHg

91. 2)ALVEOLI TO PULMONARY
Factors important in efficient respiratory exchange between
alveolar air and capillary blood in the lung
1. A large PO2 gradient of approximately 100- 40 mm Hg.
2. A large surface area available for gas exchange with a thin diffusion
barrier.
3. A favorable diffusion coefficient for oxygen.
4. Efficient binding of O2 to Hb in blood

92. ❖ O2moves across the alveolar membranes into the pulmonary
capillaries by passive diffusion , across the alveolo-capillary
membrane, through the plasma and across the erythrocyte
membrane and binds to Hb.
This is ‘‘driven’’ by a partial-pressure gradient for oxygen
(pAO2 – pO2)

94. MOVEMENT OF O2 DOWN
CONCENTRATION
GRADIENT

95. OXYGEN CASCADE
• Oxygen moves down the
concentration gradient from a relatively
high level in air to that in the cell
• The PO2reaches the lowest level (4-
20 mmHg) in the mitochondria
❖ This decrease in PO2 from air to
the mitochondrion is known as the
OXYGEN CASCADE

96. PAO2
❖ PAO2 = PiO2 ‒ PA CO2/R
*Where, PIO2 is inspired oxygen tension,
PACO2 is alveolar CO2 tension (assumed to equal arterial
PCO2), R is the respiratory exchange ratio (normally in the
range of 0.8 to 1.0),
*The alveolar oxygen tension is approximately 104mm of Hg
❖ The factors that determine the precise value of alveolar
PO2 are
(1)the PO2 of atmospheric air,
(2) the rate of alveolar ventilation, and
(3) the rate of total body oxygen consumption

97. PaO2
❖ PaO2cannot be calculated like PAO2but must be measured at
room air. Arterial O2tension can be approximated by the
following formula (in mm Hg):
❖ PaO2=102-age/3.
❖ The normal PaO2: 97mm Hg

98. PA02 – Pa02
❖ The Alveolar–arterial gradient is a measure of the
difference between the alveolar concentration (A) and the
arterial (a) concentration of oxygen. It is used in diagnosing
the source of hypoxemia. It helps to assess the integrity of
alveolar capillary unit
❖ normally about 5–10 mm Hg, but progressively increases
with age up to25 mm Hg
❖ A high A–a gradient could indicate a patient breathing hard to
achieve normal oxygenation.If lack of oxygenation is
proportional to low respiratory effort, then the A–a gradient is
not increased

99. Exchange of gases In Alveoli-
HENRY’S LAW
❖ When a liquid is exposed to air containing a particular gas,
molecules of the gas will enter the liquid and dissolve in it.
❖ Henry’s law states that “the amount of gas dissolved in a
liquid will be directly proportional to the partial pressure of
the gas in the liquid-gas interface”.
❖ As long as the PO2 in the gas phase is higher than the PO2 in
the liquid phase, there will be a net diffusion of O2 into the
blood.
❖ Diffusion equilibrium will be reached only when the PO2 in
the liquid phase is equal to the PO2 in the gas phase.

100. Partial pressures of carbon dioxide and oxygen in inspired air at
sea level and various places in the body

101. Diffusion of gases across
Respiratory Membrane
❖ Respiratory Unit is composed of a respiratory
bronchiole, alveolar ducts, atria, and alveoli.
The alveolar walls are extremely thin, and between the alveoli
is an almost solid network of interconnecting capillaries & the
alveolar gases are in very close proximity to the blood of the
pulmonary capillaries

102. Respiratory Membrane: Gas
exchange between the alveolar
air and the pulmonary blood
occurs through the membranes
of all the terminal portions of
the lungs. All these membranes
are collectively known as the
respiratory membrane, also
called the pulmonary
membrane.

103. Factors That Affect the Rate of Gas
Diffusion Through the Respiratory
Membrane
❖ The thickness of the respiratory membrane :The rate of diffusion
through the membrane is inversely proportional to the thickness of the
membrane and any factor that increases the thickness (eg. Fibrosis,
oedema fluid) can interfere significantly with normal respiratory
exchange of gases.
❖ The surface area of the respiratory membrane: Greater the surface
area greater is the rate of diffusion. In emphysema, the total surface area
of the respiratory membrane is often decreased because of loss of the
alveolar walls and respiratory exchange of gases is impeded.
❖ The diffusion coefficient for transfer of each gas through the
respiratory membrane depends on the gas’s solubility in the membrane
and, inversely, on the square root of the gas’s molecular weight.
❖ The Alveolar–arterial gas gradient.

104. Diffusion from Alveoli to
Pulmonary capillary

105. Rate of gas diffusion =
Diffusion coefficient X Pressure gradient x Surface area of
the membrane
Thickness of the membrane
-The volume of gas transfer across the alveolar-capillary
membrane per unit time is:
Directly proportional to
❖The difference in the partial pressure of gas between alveoli
and capillary blood.
❖The surface area of the membrane. The solubility of the gas.

106. Contd.
❖ Inversely Proportional to :
-Thickness of the membrane.
-Molecular weight of the gas.

107. Diffusing Capacity Of
Respiratory Membrane
❖ The volume of a gas that will diffuse through the membrane
each minute for a partial pressure difference of 1 mm Hg.
❖ In an average young man, the diffusing capacity for oxygen
under resting conditions averages 21 ml/min/mm Hg.
❖ The mean oxygen pressure difference across the respiratory
membrane during normal, quiet breathing is about 11 mm Hg.
Multiplication of this pressure by the diffusing capacity (11 ×
21) gives a total of about 230 milliliters of oxygen diffusing
through the respiratory membrane each minute
❖ This is equal to the rate at which the resting body uses
oxygen.

108. 3) PULMONARY TO SYSTEMIC
CAPILLARIES
❖ Each liter normally contains the number of oxygen molecules
equivalent to 200 ml of pure gaseous oxygen at atmospheric pressure.
❖ The oxygen is present in two forms:
(1) dissolved in the plasma
(2) reversibly combined with hemoglobin molecules in the RBCs.
❖ O2 is relatively insoluble in water, only 3 ml can be dissolved in 1 L
of blood at the normal arterial PO2 of 100 mmHg. The other 197 ml of
oxygen in a liter of arterial blood, more than 98 percent of the oxygen
content in the liter, is transported in the erythrocytes reversibly
combined with hemoglobin.

109. Oxygen
Transport
Carried in blood :
1. By red blood cells
 Bound to Hb
 97-98%
2. Dissolved O2 in plasma
 Obeys Henry’s law
PO2 x a = O2 conc in sol
a = Solubility Coefficient (0.003mL/100mL/mmHg at 37C)
Low capacity to carry O2
Bound to Hgb
Dissolved

110. HEMOGLOBIN
❖ Consists of Four Heme and Four
Protein subunits
❖ Heme : Iron- Porphyrin compound
❖ Adult HB : 2 alpha AND 2 beta
subunits
❖ Each gm HB carries 1.34 ml of O2
(upto 1.39ml)

111. CHEMICAL BINDING OF
HEMOGLOBIN & OXYGEN
*Hemoglobin combines reversibly with O2
*Association and dissociation of Hb & O2 occurs
within milliseconds
– Critically fast reaction important for O2 exchange
Very loose coordination bonds between Fe2+ and O2,
easily reversible
•Oxygen carried in molecular state (O2) not ionic O2-

112. Oxygen Saturation &
Capacity
• Up to four oxygen molecules can bind to
one hemoglobin (Hb)
• Ratio of oxygen bound to Hb compared to
total amount that can be bound is Oxygen
Saturation
• Maximal amount of O2 bound to Hb is
defined as the Oxygen Capacity

113. Effect of PO2 on Hemoglobin
Saturation: The O2-Hb Dissociation
Curve
The oxygen–hemoglobin dissociation curve plots the proportion
of Hb in its saturated form on the vertical axis against the
prevailing O2 tension on the horizontal axis Important tool for
understanding how blood carries and releases oxygen. More
specifically it relates between the percentage of O2 carrying
capacity of Hb and PaO2

114. ODC
It is a S shaped curve with
*upper flat (plateau) part.
*Lower steep Part

115. ODC Contd.
❖ The curve is S-shaped because each Hb molecule contains
four subunits;
each binding of O2 to each subunit facilites the binding of the
next one.
❖ TThis Combiantion of oxygen with hemoglobin is an example
of cooperativity

116. Contd.
❖ The globin units of DeoxyHb are tightly held by
Electrostatic bonds in a conformation with a relatively
low affinity for Oxygen
❖ The binding of Oxygen to a heme molecule breaks
these bonds leading to conformation change such that
the Remaining oxygen binding sites are exposed .
❖ Thus , the binding of one O2 molecule to DeoxyHb
increases affinity of the remaining sites on the same Hb
and so on

117. Significance of the S-shape
curve
100%
% saturation of
haemoglobin
Plateau:
► haemoglobin highly saturated with O2
favour the loading of O2 in lung
Steep slope:
►small drop of O2 partial pressure leads to a rapid decrease in
% saturation of haemoglobin
►favour the release of O2 in tissue cells
partial pressure
of O2 (mmHg)

118. Steep Portion of
Curv
e
.
• “Dissociation Portion” of
curve.
• Between 10 and 60 mm Hg.
• Small increases in PO2 yield
large increases in SO2.
• At the tissue capillary, blood
comes in contact with reduced
tissue PO2 and oxygen diffuses
from the capillary to the tissue.

119. Flat Portion Of Curve
• “Association Portion” of curve.
• Greater than 60 mm Hg.
• Large increases in PO2 yield small increases in SO2.
• At the pulmonary capillary, blood comes in contact with
increased alveolar PO2 and oxygen diffuses from the alveolus
to the capillary ,As the PO2 rises, oxygen binds with the
hemoglobin (increasing SO2).
• Very little rise in oxygen saturation above 100 mm Hg of
PaO2.

120. P50
• The partial pressure of oxygen in the blood at which the
haemoglobin is 50% saturated, is known as the P50.
• The P50 is a conventional measure of haemoglobin affinity
for oxygen
• Normal P50 value is 26.7 mm Hg
• As P50 increases/decreases, we say the “curve has shifted”.
– P50 less than 27: Shift to the left.
– P50 greater than 27: Shift to the right.

121. Rules of Thumb of
the Oxyhemoglobin
Curve
PO2 SO2
27 50
40 75
60 90
250 100
PO2 SO2
40 70
50 80
60 90

122. 2727
RIGHT SHIFT
LEFT SHIFT
Decreasing P50.
Increasing P50

123. Factors affecting
Dissociation
BLOOD TEMPERATURE
•increased blood temperature
•reduces haemoglobin affinity for O2
BLOOD Ph
•lowering of blood pH (making blood
more acidic)
•caused by presence of H+ ions from lactic
acid or carbonic acid
•reduces affinity of Hb for O2
CARBON DIOXIDE CONCENTRATION
•the higher CO2 concentration in tissue
•the less the affinity of Hb for O2

124. EFFECT OF PH
❖ H+ decreases the affinity of Hb molecule for O2 . It does
so by combining with the globin portion of hemoglobin
and altering the conformation of the Hb molecule.
❖ H+ and O2 both compete for binding to the hemoglobin
molecule. Therefore, with increased acidity, the
hemoglobin binds less O2 for a given PO2 (and more H+)

125. EFFECT OF CO2
CO2 affects the curve in two ways:
1
1) Most of the CO2 content (80–90%) is transported as
bicarbonate ions. The formation of a bicarbonate ion will
release a proton into the plasma. Hence, the elevated CO2
content creates a respiratory acidosis and shifts the oxygen–
hemoglobin dissociation curve to the right.
2)About 5–10% of the total CO2 content of blood is
transported as carbamino compounds which bind to Hb
forming CarbaminoHb. Levels of carbamino compounds
have the effect of shifting the curve to the left.

126. Bohr
Effect
First Described By Christian Bohr in 1904
•The effect of CO2 on the OHDC is known as the
Bohr Effect
•High PCO2 levels and low pH decrease affinity of
hemoglobin for oxygen (a right-ward shift).
•This occurs at the tissues where a high level of
PCO2 and acidemia contribute to the unloading of
oxygen.

127. Bohr effect – the effect of [CO2] on haemoglobin
100%
% saturation of
haemoglobin
partial pressure
of O2 (mmHg)
Lower [CO2]
e.g. in lung
►curve shift
to the left
haemoglobin
has a higher
affinity to O2
Higher [CO2] e.g. tissue cells
► curve shift to the right
►haemoglobin has a lower
affinity to O2
2

128. IMPLICATIONS OF BOHR
EFECT
• Enhance oxygenation of blood in lungs and to
enhance release of O2 in the tissues
In lungs, CO2 diffuses out of the blood (Dec. H+ conc
due to Dec. in H2CO3 conc)
Shift of O2-Hb curve to left
Inc.O2 bound to HbInc. O2 transport to tissues
In tissue capillaries,
Inc. CO2 & H+ greater release of O2 due to less avid
binding of O2 to Hb.

129. DOUBLE BOHR EFFECT
FETAL BLOOD MATERNAL BLOOD
Loss of CO2 Gain of CO2
Rise in pH Fall in pH
Leftward Shift of ODC Rightward shift of ODC
• Reciprocal changes in acid - base balance that occur in maternal & fetal blood in transit
through the placenta

130. Oxygen dissociation
curve: Foetal VS
Maternal
% saturation of
haemoglobin
Maternal
partial pressure
of O2 (mmHg)
Foetal
→ Foetal haemoglobin has higher affinity to O2 so as
obtain O2 from maternal blood in the placenta.

131. ROLE OF 2,3
DPG(diphosphoglycerate)
2,3 DPG is an organic phosphate normally
found in the RBC
Produced during Anaerobic glycolysis in
RBCS

132. 2,3
DPG
• Tendency to bind to β chains of Hb and thereby
decrease the affinity of Hemoglobin for oxygen.
• HbO2 + 2,3 DPG → Hb-2,3 DPG + O2
• It promotes a rightward shift and enhances oxygen
unloading at the tissues.
• This shift is longer in duration than that due to [H+],
PCO2 or temperature.
– A doubling of DPG will result in a 10 time increase in P50.

133. 2,3
DPG
• The levels increase with • The levels decrease with
– Cellular hypoxia.
– Anemia
– Hypoxemia secondary to
COPD
– Congenital Heart Disease
– Ascent to high altitudes
– Septic Shock
– Acidemia
– Stored blood
• No DPG after 2 weeks of
storage.

134. EFFECTS OF 2,3-BPG ON STORED BLOOD
• In banked blood , the 2,3-BPG level falls and the
ability of this blood to release O2 to the tissues is
reduced.
• less if blood is stored in citrate–phosphate–
dextrose solution than acid–citrate–dextrose
solution.

135. Effects of anemia & CO on
the oxyhemoglobin dissociation curve
Anemia
• ↓OCC of blood & O2 content;
• SaO2 remains normal
Carbon Monoxide [CO]
• affinity of Hb for CO is 250
fold relative to O2 competes
with O2 binding
• L shift- interfere with O2
unloading at tissues
• severe tissue hypoxia
• sigmoidal HbO2 curve becomes
hyperbolic
CHANGES THE SHAPE OF
OHDC

136. OXYGEN MYOGLOBIN
CURVE
❖ One molecule of myoglobin has one ferrous Atom (HB
has 4 ferrous )
❖ One MGB combines with One O2
❖ O2- Myoglobin Curve is rectangular and to the left of
ODC
❖ It gives oxygen to tissues at very low PO2
❖ Acts as O2 store used in severe muscular exercise
when PO2 is very low

138. 4) CAPILLARIES TO CELLS
The blood entering the capillary with a high PO2 begins to
surrender its oxygen because it is surrounded by an immediate
environment of lower PO2, initially giving off oxygen dissolved
in plasma, and followed by release of oxygen bound to Hb.
The principal force driving diffusion is the gradient in pO2 from
blood to the cells
The oxygen dissociation characteristics of Hb facilitate the rapid
and efficient unloading of oxygen within the capillary.
The O2ultimately diffuses from the microcirculation into the cells
and finally into the mitochondria.

140. OXYGEN CONTENT
❖ Total amount of O2 present in 100 ml of Arterial Blood CaO2=Hb. Bound
O2+ dissolved Hb
= [1.34 x Hb x SaO2] + 0.003 x PO2
= [1.34×15×97.5] +0.003×100
=19.9=20ml /dl approx
=200ml/L
Similarly for Venous blood
CvO2=1.34 × Hb × SvO2 + 0.003 × PvO2
replacing with values we have CvO2=15 ml/dl
=150 ml/L

141. DELIVERY OF OXYGEN
❖ Quantity of O2 made available to body in one minute – O2 delivery or flux
❖ DO2= Q × CaO2 × 10
= Q × 1.34 × Hb × SaO2 × 10
Q - cardiac output
CaO2-arterial oxygen content
Multiplier 10 is used to convert CaO2 from ml/dl to ml/L
❖ Normal DO2 in adults at rest is 900-1,100 ml/min

142. O2 DELIVERY DURING
EXERCISE
1. During strenuous exercise VO2 may to 20
times N
2. Blood also remains in the capillary for <1/2
N time due to Inc Cardiac Output
3. O2 Sat not affected
4. Blood fully sat in first 1/3 of N time
available to pass through pul circulation

143. • Diffusion capacity Inc. upto 3 fold since:
1.Additional capillaries open up Inc. no of
capillaries participating in diffusion process
2.Dilatation of both alveoli and capillaries Dec.
alveolo-capillary distance
3. Improved V/Q ratio in upper part of lungs due
to Inc. blood flow to upper part of lungs

145. OXYGEN DELIVERY IN CRITICAL
ILLNESS
• Tissue hypoxia is due to disordered
regional distribution of blood flow
• often caused by capillary
microthrombosis after endothelial
damage and neutrophil activation
rather than by arterial hypoxaemia

146. OXYGEN CONSUMPTION-
V02
❖ Total amount of O2 consumed by the tissues per unit of
time
❖ VO2=Q × (CaO2- CvO2) × 10
❖ rearranging, VO2=Q × 1.34 × Hb × (SaO2-SvO2)
Substituting the values
❖ Normal resting O2 consumption ~ 200 to 300 ml/min
in adult humans

147. 19
OXYGEN EXTRACTION
RATIO
• The oxygen extraction ratio (O2ER) is the amount of oxygen
extracted by the peripheral tissues divided by the amount of
O2 delivered to the peripheral cells.
• Index of efficiency of O2 transport
• aka: Oxygen coefficient ratio & Oxygen utilization ratio
– O2ER = VO2 / DO2
– When SaO2 ~1 :
O2ER ~ SaO2-SvO2
– Normally ~ 25% but to 70-80% during maximal
exercise in well trained athletes

148. Factors that affect
O2ER
•Increased with:
•Decreased CO
•Increased VO2
•Exercise
•Seizures
•Shivering
•Hyperthermia
•Anemia
•Low PaO2
•Decreased with:
•Increased Cardiac Output
•Skeletal Muscle Relaxation
•Peripheral Shunting
•Certain Poisons
•Hypothermia
•Increased Hemoglobin
•Increased PaO2

149. •In general, DO2 >>
VO2
•When oxygen
consumption is high
(exercise) the ↑ed O2
requirement is usually
provided by an ↑ed CO
•Alternatively, if oxygen
delivery falls relative to
oxygen consumption the
tissues extract more
oxygen from the hb (the
saturation of mixed
venous blood falls
below 70%) (a-b )
A reduction below point 'c' in figure cannot be
compensated for by an increased oxygen extraction and
results in anaerobic metabolism and lactic acidosis.
CRITICALDO2

150. O2 DIFFUSION FROM
INTERSTITIUM TO
CELLS
Intracellular PO2 < Interstitial fluid PO2
•O2 constantly utilized by the cells
•Cellular metabolic rate determines overall O2
consumption
N PcO2 ~ 5-40 mm Hg (average 23 mmHg)
N intracellular req for optimal maintenance of
metabolic pathways ~ 3 mm Hg

151. Pasteur
point –
 critical mitochondrial PO2 below which aerobic
metabolism cannot occur
 0.15 – 0.3 kPa = 1.4 – 2.3mmHg

152. DO2 – VO2 relationship in critically
ill
Slope of maximum OER is
less steep
↓
Reduced extraction of
oxygen by tissues
↓
Does not plateau
(consumption remains
supply dependent even
at “supranormal” levels
of DO2)

153. EFFECTS OF
ANAESTEHSIA

154. THE EFFECTS OF
ANAESTHESIA
• The normal protective response to hypoxia is
reduced by anaesthetic drugs and this effect extends
into the post-operative period.
• Following induction of anaesthesia : FRC ↓
• V/Q mismatch is ↑ed
• Atelectasis develops rapidly
• This 'venous admixture' increases from N 1% to
around 10% following induction of anaesthesia.

155. Contd.
• Volatile anaesthetic agents suppress hypoxic
pulmonary vasoconstriction.
• Many anaesthetic agents depress CO and therefore ↓
• O2 delivery.
• Anaesthesia causes a 15% ↓ in metabolic rate and
therefore a reduction in oxygen requirements.
• Artificial ventilation causes a further 6% ↓ in
oxygen requirements as the work of breathing is
removed.

156. OXYGEN STORES
• o2 stores are limited to lung and blood.
• The amount of O2 in the lung is dependent on
the FRC and the alveolar concentration of
oxygen.
• Breathing 100% oxygen causes a large increase
in the total stores as the FRC fills with oxygen
• This is the reason why pre-oxygenation is so
effective.

157. CO2 TRANSPORT

158. ❖ At each point in gas transport chain, CO2 diffuses in
exactly the opposite direction to O2 diffusion.
❖ CO2 diffuses 20 times as rapidly as O2.
❖ Pressure differences required for CO2 diffusion are far
less than those required to cause O2 diffusion
❖ PCO2 of venous blood=45mmhg(6.1kPa)
❖ Whereas in Alveoli PCO2=40mmhg(5.3kPa)
A pressure gradient of 5mmhg drives CO2 across alveolar
membrane.
CO2 DIFFUSION

159. ❖ Carbon dioxide is transported in the blood from the
tissue to the lungs in three ways:
(i) In dissolved form;
(ii) As bicarbonate;
(iii) bound to proteins, particularly haemoglobin
(carbamino-Hb)
❖ 75% is transported in the red blood cell
❖ 25% is transported in the plasma.
CO2 TRANSPORT IN BLOOD

160. 1) DISSOLVED CO2
❖ CO2 is more soluble in blood than O2
❖ Solubility coefficient of CO2 = 0.067ml/mmhg

161. 2) AS BICARBONATE

163. Chloride Shift

164. • Most of H+ combine with Hb because reduced Hb is less acidic
so better proton acceptor
• This fact that deoxygenation of the blood inc its ability to carry
CO2 is known as HALDANE EFFECT.
• As a result of the shift of chloride ions into the red cell and the
buffering of hydrogen ions onto reduced haemoglobin, the
intercellular osmolarity increases slightly an →→ water
enters causing the cell to swel →→ an increase in mean
corpuscular volume (MCV)..
• Hematocrit of venous blood is 3%>arterial
• Venous RBC are more fragile
• Cl content of RBCs V>A

165. 3) CO2 BOUND AS CARBAMINO COMPOUND
❖ Some of CO2 in RBCs reacts with amino group Of HB
and other protiens forming Carbamino compunds
❖ DeoxyHB binds more H+ and forms Carabmino
compounds more readily.
❖ Consequently Venous Blood carries more C02 than
Arterial blood
❖ CO2 uptake is facilitated in tissue and CO2 release is
facilitated in lungs
❖ About 11% of CO2 added to blood in the systemic
capillaries is carried to lungs as Carbamino compounds

167. CARBONDIOXIDE
DISSOCIATION CURVE

168. THANK YOU !