This document provides an overview of respiratory physiology. It discusses the processes of external and internal respiration, ventilation, lung volumes and capacities, pressures and gradients, spontaneous and positive pressure ventilation, lung characteristics, compliance, elastic forces, surface tension, surfactant, ventilation, perfusion, gas tensions, the oxygen cascade, oxygen transport via dissolved oxygen and hemoglobin, and factors affecting hemoglobin dissociation.

1. RESPIRATORY PHYSIOLOGY
Presenter : Dr Pratik Tantia

2. RESPIRATION
• Respiration involves the exchange of O2 and CO2 between
an organism and its environment.
• External respiration exchange between alveoli and
pulmonary capillaries.
• Internal respiration cellular level O2 from
blood into cells. CO2 is produced by this aerobic
metabolism cells to systemic capillaries.

3. External Respiration
Internal Respiration

4. VENTILATION
• Ventilation is the movement of air into and out of the
lungs.
• Spontaneous ventilation contraction of the muscles
of inspiration (diaphragm and external intercostals)
expansion of the thorax.
• Normal quiet exhalation is passive and does not require
any work.
• Maximal spontaneous inspiration or expiration
accessory muscles.

5. FUNCTIONAL ANATOMY

6. FUNCTIONAL ANATOMY

7. PRESSURES AND GRADIENTS

8. SPONTANEOUS VENTILATION

9. POSITIVE PRESSURE VENTILATION

10. LUNG VOLUMES AND CAPACITIES

11. LUNG CHARACTERISTICS
• Normally, two types of forces oppose inflation of the
lungs: elastic forces and frictional forces.
• Elastic forces arise from the elastic properties of the
lungs and chest wall.
• Frictional forces are the result of two factors: the
resistance of the tissues and organs and resistance to gas
flow through the airways.

12. HYSTERESIS

13. ELASTIC FORCES
• 1. Elastic resistance of lung tissue and chest wall :
Compliance and Elastance
• 2. Resistance from surface forces at the alveolar gas-
liquid interface : Surface tension
• Much of the elastic recoil is due to the surface tension
acting throughout the vast air/water interface lining the
alveoli, as shown by von Neergard by comparing the
elastance of lung filled with air and lung filled with water.

14. COMPLIANCE
• Compliance the relative ease with which a structure
distends.
• Elastance tendency of a structure to return to its
original form after being stretched.
• Thus, C = 1/e or e = 1/C.
• Compliance of the respiratory system is determined by
measuring the change (Δ) of volume (V) that occurs when
pressure (P) is applied to the system: C = ΔV/ ΔP.

15. COMPLIANCE
• Static compliance : relationship between volume change
of lung and the transpulmonary pressure change
measured under known static conditions (zero airflow).
• Dynamic compliance : measurements are made during
rhythmic breathing, but compliance is calculated from
pressure and volume measurements made when no gas
is flowing, usually at end-inspiratory and end-expiratory
‘no-flow’ points.

16. STATIC VS DYNAMIC

17. CALCULATING COMPLIANCE

18. VALUES
• In spontaneously breathing individual, total respiratory
system compliance is about 100 (50-170) mL/cm H2O.
• For intubated and mechanically ventilated patients with
normal lungs and a normal chest wall, compliance varies
from 40 to 50 mL/cm H2O in men and 35 to 45 mL/cm
H2O in women to as high as 100 mL/cm H2O in either
gender.

19. FACTORS AFFECTING COMPLIANCE
• Lung Compliance
– Lung volume (Specific
compliance)
– Age
– Posture
– Pulmonary blood
volume
– Bronchial smooth
muscle tone
– Disease states
• Thoracic Compliance
– Age
– Posture
– Skin lesions (burns)
– Obesity
– Abdominal distension
– Kyphoscoliosis

20. SURFACE TENSION
• The gas–fluid interface lining the alveoli causes them to
behave as bubbles. Surface tension forces tend to reduce
the area of the interface and favor alveolar collapse.
• Laplace Equation :
• To prevent the alveoli from collapsing, a transmural
pressure should be acting across the alveolar wall.
• This pressure, for a single alveolus, is equal to 2 X surface
tension / radius of the alveolus (2T/r).

21. SURFACE TENSION AND SURFACTANT
• Surface-active
substance called
Surfactant.
• The ability of
surfactant to lower
surface tension is
proportional to its
concentration within
the alveolus.
• It thus acts to stabilize
the alveolar size.

22. SURFACTANT SYNTHESIS
• Surfactant is both formed in and liberated from the
alveolar epithelial type II cell.
• The lamellar bodies contain stored surfactant that is
released into the alveolus by exocytosis in response to high
volume lung inflation, increased ventilation rate or
endocrine stimulation.
• After release, surfactant initially forms a lattice structure
termed tubular myelin, which is then reorganized into
monolayered or multilayered surface films.
• Main constituents are DPPC, a phospholipid and Surfactant
proteins (SP) A-D.

23. ALVEOLAR INTERDEPENDENCE
When an alveolus in a group of alveoli collapses, the
surrounding alveoli are stretched. As the other alveoli
recoil in resistance, they pull outward on the collapsing
alveolus.

24. FRICTIONAL FORCES
• Resistance is a measurement of the frictional forces that
must be overcome during breathing.
• This non-elastic resistance is due to
– Resistance to airflow ~ 80%
– Tissue viscous resistance ~ 20%

25. AIRWAY RESISTANCE
• Poiseuille’s law
• The diameter of airway lumen and flow of gas into the
lungs can decrease as a result of bronchospasm,
increased secretions, mucosal edema, or kinks in the
endotracheal tube.

26. AIRWAY RESISTANCE
• The relationship of gas flow, pressure, and resistance in
the airways is described by the equation for airway
resistance,
Raw = Pta/flow, Pta = PIP-Pplat
• In normal, conscious individuals with a gas flow of 0.5
L/s, resistance is about 0.6 to 2.4 cm H2O/(L/s).
• The actual amount varies over the entire respiratory
cycle. The variation occurs because flow during
spontaneous ventilation usually is slower at beginning
and end of the cycle and faster in the middle.

27. TISSUE RESISTANCE
• Due mainly to the movement of pleural layers between
lobes, and between the lungs and chest wall during
inspiration & expiration.
• Tissue viscous resistance remains constant under most
circumstances.
• For example, an obese patient or one with fibrosis has
increased tissue resistance, but the tissue resistance
usually does not change significantly when these patients
are mechanically ventilated.

28. WORK OF BREATHING
• It is the work required by the respiratory muscles to
overcome the mechanical impedance to respiration.
• The physical work of breathing can be divided into
– Resistance work
– Compliance work

29. RESISTANCE WORK
• Raw = ΔP/V
(Raw= Airway resistance, ΔP = PIP-Pplat and V= Flow )
• The pressure change ΔP amount of work imposed on
the patient.
• If WOB remains constant increase in the airway
resistance decrease the flow.
• If a patient is unable to overcome the airway resistance
by increasing WOB hypoventilation.

30. COMPLIANCE WORK
• C = ΔV/ΔP
• If the change in pressure remains constant decrease
in compliance decrease in the tidal volume and thus
minute ventilation.
• In low compliance situations such as ARDS, the decrease
in minute ventilation is characterized by low tidal volume
and high respiratory rates.
• In the clinical setting, atelectasis is one of the most
frequent causes of increased WOB.

31. WORK OF BREATHING
• Triangle APAE represents
the Compliance work.
• Area ACBPA represents
Inspiratory Resistance
work.
• Triangle APAD
represents Expiratory
Resistance work.
• The area within the
hysteresis represents
total Resistance work.

32. TIME CONSTANTS
• Regional differences in compliance and resistance exist
throughout the lungs.
• That is, the compliance and resistance values of a
terminal respiratory unit (acinus) may be considerably
different from those of another unit.
• Thus the characteristics of the lung are heterogeneous,
not homogeneous.
• Alterations in C and Raw affect how rapidly lung units fill
and empty.

33. TIME CONSTANTS

34. TIME CONSTANTS
• Calculation of time constants is important when setting the
ventilator’s inspiratory and expiratory time.
• Ti less than 3 time constants may result in incomplete
delivery of tidal volume.
• Prolonging the Ti allows even distribution of ventilation
and adequate delivery of tidal volume.
• Te less than 3 time constants may lead to incomplete
emptying of lungs.
• This can increase the FRC and cause trapping of air in the
lungs.

35. VENTILATION
• Ventilation is usually measured as the sum of all exhaled
gas volumes in 1 minute.
• Minute ventilation = RR x Tidal volume
• Not all the inspired gas mixture reaches alveoli; some of
it remains in the airways and is exhaled without being
exchanged with alveolar gases.
• Alveolar ventilation is the volume of inspired gases
actually taking part in gas exchange in 1 minute.

36. DEAD SPACE
• That part of the VT not participating in alveolar gas
exchange is known as dead space (VD).
• Dead space is actually composed of gases in non-
respiratory airways (Anatomic dead space) as well as in
alveoli that are not perfused (Alveolar dead space).
• Sum of the two is referred to as Physiological dead space.
• In the upright position, dead space is normally about 150
mL for most adults (approximately 2 mL/kg) and is nearly
all anatomic.

37. DISTRIBUTION OF VENTILATION

38. PERFUSION
• Of the approximately 5 L/min of blood flowing through
the lungs, only about 70–100 mL at any one time is within
the pulmonary capillaries undergoing gas exchange.
• At the alveolar–capillary membrane, this small volume
forms a 50–100 m2 sheet of blood approximately one red
cell thick.
• Hypoxia is a powerful stimulus for pulmonary
vasoconstriction.
• Hypoxic pulmonary vasoconstriction is an important
physiological mechanism in reducing intrapulmonary
shunting and preventing hypoxemia.

39. DISTRIBUTION OF PERFUSION

40. DISTRIBUTION OF PERFUSION
• Zone 1 is not observed in the normal lung; only observed
with positive pressure ventilation. This becomes the
alveolar dead space.
• Zone 2 is the part of lung about 3 cm above heart. In this
region blood flows in pulses. At first there is no flow
because of obstruction at the venous end. Pressure from
the arterial side builds up until it exceeds alveolar pressure
and flow resumes (Waterfall effect).
• Zone 3 comprises the majority of the lungs in health. Blood
flow is continuous throughout the cardiac cycle. Flow is
determined by the Ppa-Ppv difference, which is constant
down this portion of the lung.

41. DISTRIBUTION OF PERFUSION
• Zone 4 can be seen at the lung bases at low lung volumes
or in pulmonary edema.
• Pulmonary interstitial pressure (Pi) rises as lung volume
decreases due to reduced radial tethering of the
lung parenchyma.
• An increase in Pi causes extralveolar blood vessels to
reduce in caliber and so blood flow decreases.
• Flow in zone 4 is governed by the arterio-interstitial
pressure difference (Pa − Pi).

42. VENTILATION/PERFUSION RATIO
• Because alveolar ventilation is normally about 4 L/min and
pulmonary capillary perfusion is 5 L/min, the overall V/Q
ratio is about 0.8.
• V/Q for individual lung units (each alveolus and its
capillary) can range from 0 (no ventilation) to infinity (no
perfusion); the former is referred to as intrapulmonary
shunt, whereas the latter constitutes alveolar dead space.
• Because perfusion increases at a greater rate than
ventilation, nondependent (apical) areas tend to have
higher V/Q ratios than do dependent (basal) areas.

43. V/Q RATIO

44. SHUNT
• Shunting denotes the process whereby desaturated,
mixed venous blood from the right heart returns to the
left heart without being oxygenated in lungs.
• Intrapulmonary shunts are often classified as absolute or
relative.
• Absolute shunt refers to anatomic shunts and lung units
where V/Q is 0.
• A relative shunt is an area of lung with a low but finite
V/Q ratio.
• Clinically, hypoxemia from a relative shunt can usually be
partially corrected by increasing FiO2; hypoxemia caused
by an absolute shunt cannot.

45. VENOUS ADMIXTURE
• Venous admixture is the amount of mixed venous blood
that would have to be mixed with pulmonary end-
capillary blood to account for the difference in O2 tension
between arterial and pulmonary end-capillary blood.
• Pulmonary end-capillary blood is considered to have the
same concentrations as alveolar gas.
• Venous admixture is usually expressed as a fraction of
total cardiac output QS/QT.
• The equation may be derived with the law for the
conservation of mass for O2 across the pulmonary
capillary bed.

46. VENOUS ADMIXTURE
•Normal QS/QT is primarily due to communication
between deep bronchial veins and pulmonary veins, the
Thebesian circulation in the heart, and areas of low but
finite V/Q in the lungs.
•Venous admixture in normal individuals (physiological
shunt) is typically less than 5%.

47. GAS TENSIONS
• ALVEOLAR OXYGEN TENSION (PAO2)
• PULMONARY END-CAPILLARY OXYGEN TENSION(Pc’O2)
• ARTERIAL OXYGEN TENSION (PaO2)
– The A–a gradient for O2 is directly proportional to shunt
but inversely proportional to mixed venous O2 tension.
• MIXED VENOUS OXYGEN TENSION (PvO2)
– Normal PvO2 is about 40 mm Hg and represents the
overall balance between O2 consumption and delivery.

48. GAS TENSIONS
• MIXED VENOUS CO2 TENSION (PvCO2)
– Normal PvCO2 is about 46 mmHg and is end result of
mixing of blood from tissues of varying metabolic
activity.
• ALVEOLAR CO2 TENSION (PACO2)
– PACO2 = VCO2 / VA
• PULMONARY END-CAPILLARY CO2 TENSION(Pc’CO2)
• ARTERIAL CO2 TENSION (PaCO2)
• END-TIDAL CO2 TENSION (PETCO2)
– The PACO2–PETCO2 gradient is normally less than 5 mmHg
and represents dilution of alveolar gas with CO2-free gas
from non-perfused alveoli (alveolar dead space).

49. OXYGEN CASCADE
• The Po2 of dry air is 159 and humidified air is 149 mmHg
at sea level.
• Oxygen moves by mass transport and down partial
pressure gradients from the inspired air to the
mitochondria where it is consumed. At this point, the Po2
is about 3.8–22.5 mmHg.
• The steps by which the Po2 decreases from air to the
mitochondria are known as the Oxygen Cascade.
• Any one step in the cascade may be increased under
pathological circumstances and may result in hypoxia.

50. OXYGEN CASCADE

51. OXYGEN TRANSPORT
• Oxygen is carried in the blood in two forms
1. dissolved in solution and
2. in reversible association with hemoglobin.

52. DISSOLVED OXYGEN
• Henry’s Law,
Gas concentration = α x partial pressure
where α = the gas solubility coefficient for a given
solution at a given temperature
• The solubility coefficient for O2 at normal body
temperature is 0.003 mL/dL per mmHg.
• Even with a PaO2 of 100 mmHg, the maximum amount of
O2 dissolved in blood is very small (0.3 mL/dL) compared
with that bound to hemoglobin.

53. HEMOGLOBIN

54. Hb DISSOCIATION CURVE

55. FACTORS AFFECTING
• P50 is the O2 tension at which
Hb is 50% saturated.
• Each factor shifts the
dissociation curve either to
the right (increasing P50) or to
the left (decreasing P50).
• A rightward shift lowers O2
affinity, displaces O2 from Hb
and makes more O2 available
to tissues.
• The normal P50 in adults is
26.6 mmHg.

56. EFFECTS
• Bohr Effect : An increase in blood [H+] reduces O2
binding to Hb. The result is facilitation of O2 release to
tissue with little impairment in O2 uptake.
• The influence of CO2 tension on Hb affinity for O2 is
secondary to the associated rise in [H+] when CO2
tension increases.
• The high CO2 content of venous capillary blood (by
decreasing Hb affinity for O2) facilitates the release of O2
to tissues; conversely, the lower CO2 content in
pulmonary capillaries increases Hb affinity for O2 again,
facilitating O2 uptake from alveoli.

57. OXYGEN CONTENT

58. OXYGEN TRANSPORT
• O2 transport is dependent on both respiratory and
circulatory function.
• Fick Equation
• Oxygen Extraction Ratio (O2ER)
O2ER = VO2/DO2
O2ER = CaO2-CvO2/CaO2
• The O2ER is normally about 0.25 (range = 0.2–0.3).

59. CONTROL OF OXYGEN UPTAKE
• When DO2 is moderately
reduced, VO2 remains normal
because of increased O2ER.
• With further reductions in
DO2, a critical point is reached
beyond which VO2 becomes
directly proportional to DO2.
• This state of supply-
dependent O2 is typically
associated with progressive
lactic acidosis caused by
cellular hypoxia.

60. CO2 TRANSPORT
• Carbon dioxide is
transported in blood in
three forms: dissolved in
solution, as bicarbonate,
and with proteins in the
form of carbamino
compounds . The sum of
all three forms is the total
CO2 content of blood.

61. BICARBONATE
• Mainly in RBCs and endothelium, where Carbonic
anhydrase greatly accelerates the reaction.
• On the venous side of systemic capillaries, CO2 enters
RBCs and is converted to bicarbonate, which diffuses out
of RBCs into plasma; chloride ions move from plasma
into RBCs to maintain electrical balance.
• In the pulmonary capillaries, the reverse occurs: chloride
ions move out of RBCs as bicarbonate ions re-enter for
conversion back to CO2, which diffuses out into alveoli.
• This sequence is referred to as the Chloride or
Hamburger shift.

62. CARBAMINO COMPOUNDS
• At physiological pH, only a small amount of CO2 is carried
in this form, mainly as carbaminoHb.
• Deoxygenated Hb has a greater affinity (3.5 times) for
CO2 than does oxygenated Hb.
• As a result, venous blood carries more CO2 than arterial
blood (Haldane effect).

63. HEMOGLOBIN BUFFERING
• Hb can act as a buffer at physiological pH because of its
high content of histidine. The acid–base behavior of Hb is
influenced by its oxygenation state.
• Removal of O2 from Hb in tissue capillaries causes the Hb
molecule to behave more like a base, favoring
bicarbonate formation.
• In the lungs, the reverse is true. Oxygenation of Hb favors
its action as an acid, favoring CO2 formation.

64. CONTROL OF RESPIRATION
• Spontaneous ventilation is the result of rhythmic neural
activity in respiratory centers within the brain stem.
• This activity regulates respiratory muscles to maintain
normal tensions of O2 and CO2 in the body.
• The basic neuronal activity is modified by inputs from
other areas in the brain, volutional and autonomic, as
well as various central and peripheral receptors.

65. CENTRAL RESPIRATORY CENTERS
• The basic breathing rhythm originates in the medulla.
• Two medullary groups of neurons: a dorsal respiratory
group - active during inspiration; and a ventral
respiratory group - active during expiration.
• Two pontine areas influence the dorsal (inspiratory)
medullary center.
• A lower pontine (apneustic) center is excitatory, whereas
an upper pontine (pneumotaxic) center is inhibitory.
• The pontine centers appear to fine-tune respiratory rate
and rhythm.

66. CENTRAL SENSORS
• Central chemoreceptors lie on the antero-lateral surface
of medulla and respond primarily to changes in CSF [H+].
• This mechanism is effective in regulating PaCO2, because
the blood–brain barrier is permeable to dissolved CO2
but not to HCO3–. Acute changes in PaCO2 but not in
arterial [HCO3–] are reflected in CSF; thus, a change in
CO2 results in a change in [H+].
• PaCO2 leads to CSF [H+] and activates the
chemoreceptors. Secondary stimulation of the adjacent
medullary centers increases alveolar ventilation and
reduces PaCO2 back to normal.

67. CENTRAL SENSORS
• The relationship between
PaCO2 and minute volume
is nearly linear.
• Very high PaCO2 levels
depress the ventilatory
response (CO2 narcosis).
• The PaCO2 at which
ventilation is zero is
known as the apneic
threshold.

68. PERIPHERAL SENSORS
• Peripheral chemoreceptors include the carotid bodies
and the aortic bodies.
• The carotid bodies are the principal peripheral
chemoreceptors and are sensitive to changes in PaO2,
PaCO2, pH, and arterial perfusion pressure.
• They interact with central respiratory centers via the
glossopharyngeal nerves, producing reflex increases in
alveolar ventilation in response to reductions in PaO2 and
arterial perfusion, or elevations in [H+] and PaCO2.
• Stimulated by cyanide, doxapram and large doses of
nicotine.

69. PERIPHERAL SENSORS
• Carotid bodies are most
sensitive to PaO2.
• Receptor activity does
not appreciably increase
until PaO2 decreases
below 50 mmHg.
• Anti-dopaminergic
drugs, anesthetics, and
bilateral carotid surgery
abolish the peripheral
ventilatory response to
hypoxemia.

70. PERIPHERAL SENSORS
• Stretch receptors (in the smooth muscle of airways) are
responsible for inhibition of inspiration when the lung is
inflated to excessive volumes (Hering–Breuer inflation
reflex) and shortening of exhalation when the lung is
deflated (deflation reflex).
• Irritant receptors (in the tracheobronchial mucosa) upon
activation produce reflex increases in respiratory rate,
bronchoconstriction, and coughing.
• J (juxtacapillary) receptors (in the interstitial space)
induce dyspnea in response to expansion of interstitial
space volume and various chemical mediators following
tissue damage.

71. CONTROL OF RESPIRATION

72. NON-RESPIRATORY FUNCTIONS
• Filtration : The entire cardiac output passes through the
pulmonary circulation, lungs thus act as filters preventing
emboli from passing to the left side of the circulation.
• Defence against inhaled substances : Lungs constitute a
huge interface between environment and the body and
has multiple physical, chemical and biological defence
systems against inhaled hazards.
• Metabolism : Active uptake and metabolism of many
endogenous compounds including amines, peptides and
eicosanoids.

73. THANK YOU