Factors affecting
Pulmonary Ventilation
DR. QAZI IMTIAZ RASOOL
OBJECTIVES
1.
Outline the various factors affecting airway resistance and correlate
it to changes in pulmonary ventilation.
2.
Describe the metabolism of surfactant, discuss its significance and
relate its deficiency to clinical conditions.
3.
Define compliance of the lung and chest wall, illustrate and discuss
the compliance curve and describe the effect of surfactant on it.
4.
Discuss work of breathing and relate it to clinical conditions.
Poiseuille’s Law for Pressure
1.



.
In normal inspiration, PPL falls -5 to -7.5 cm H2O, causing
bronchial airways to lengthen and to increase in diameter.
During expiration opposite
Normally not significant, however, becomes significant in
COPD.
Airway Resistance
(Raw) is defined as the pressure difference between the mouth
and the alveoli divided by the flow rate. (flow changes inversely with
1.
resistance)
1.
2.

R=P/Q
SIGNIFICANCE;The resistance that we measure in this way is the airway resistance, which
represents ∼80%. 20% represents tissue resistance-that is, the friction of
pulmonary and thoracic tissues
1.
1.
Resistance is usually insignificant because of
Large airway diameters in the first part of the conducting zone
Chief Site of Airway Resistance
1.Most of pressure drop occurs
In medium-sized bronchi ( 4-7)
2. Very small bronchioles have
very little resistance
1.
Less than 20% drop at
airways less than 2mm
2.
Paradox secondary to
prodigious number of
small airways in parallel
Rtotal=1/R1+1/R2+1/R3)
1.
Air velocity becomes
low, diffusion takes over
Factors Determining Airway Resistance
Lung Volume
1.
1.
2.
Linear relationship between lung volumes & conductance of airway resistance
As lung volume is reduced - airway resistance increases
Bronchial Smooth Muscle
2.
1.
2.
Contraction of airways increases resistance
Bronchoconstriction caused by PSN, acetylcholine, low pCO2, direct stimulation,
histamine, environmental, cold
Density & Viscosity Of Inspired Gas
3.
1.
2.
Increased resistance to flow with elevated gas density
Changes in density rather than viscosity have more influence on resistance
Resistance and Disease
1.
Asthma: Constriction of small airways, excess mucus, and histamineinduced edema
2.
Bronchitis: Long term inflammatory response causing thickened walls and
overproduction of mucous
3.
Emphysema: Collapse of smaller airways and breakdown of alveolar wall
APPLIED
Normally RAW is ∼1.5 ( 0.6 - 2.3). cm H2O/(L/s)
RAW respiratory disease can > 10 cm H2O/(L/s).
Define.
.COMPLIANCE; is the extent to which the lungs will expand
for each unit ↑ in transpulmonary pressure (if enough time is
allowed to reach equilibrium)
CL
=
∆V (liters) / ∆P (cmH2O)
200 ml/cm of H2O
Specific compliance = CL / FRC
2. Elastance
(0.08/cm H2O)
as the change in pressure per unit change in
volume and it is the reciprocal of compliance =∆P/∆V
What keeps the alveoli (lungs) expanded are:
1.
2.
Negative intra-pleural pressure
- space between 2 pleural layers is always negative or sub-atmospheric
tends to suck the lungs outward
Alveolar pressure
- pressure within the alveoli themselves tend to keep the lungs inflated
Why does an inflated lung want to recoil inward
because of surface tension- alveolus
Resists stretching
Recoils after stretch in
Favors reduced surface area (to shrink into a sphere)
Lung tissue has elastic properties
- Lung parenchyma contains both elastin and collagen fibers, proteins
-Smooth muscles are found down to level of alveolar ducts
-Through the physical principles of LaPlace’s Law
Surface tension
Size of the alveoli (bubble)
Elastic Forces of the Lung
Elastic Lung Tissue
Surface Air-fluid Interface
1.
Elastin & Collagen fibers of
lung parenchyma1/3rd
1.
2/3 rd of total elastic force in
lung is due to H2O
2.
Natural state of these
fibers is contracted coils
2.
Complex synergy between air
& fluid holds alveoli open
3.
Elastic force generated by
the return to this coiled
state after being stretched
and elongated
The recoil force assists to
deflate lungs
3.
Without air in the alveoli a fluid
filled lung has only lung tissue
elastic forces to resist volume
changes
Surfactant in the alveoli fluid
↓ST, keeps alveoli from
4.
4.
Method of P-V Curve
Measurement
V
Esophageal
Balloon
In esophagus
adjacent to
pleura
P
t
Compliance Diagram of the Lungs
1. 2 different curves accordingly as
Inspiratory compliance curve
Expiratory compliance curve
2. Compliance at low volumes
(because of difficulty with initial lung inflation)
and at high volumes
(because of the limit of chest wall expansion)
3. Total work of breathing of the cycle is the area contained in the loop.
-Tissue elastic forces = represent 1/3 of total lung elasticity
- Fluid air surface tension elastic forces in alveoli (B) = 2/3 of total lung
elasticity.
Pressure-Volume Curve
Expiration
Inspiration
Volume
Hysteresis
Non-linear curve
Pressure
Lung volumes during deflation is larger than during inflation
Trapped gas in closed small airways is cause of this higher lung volumes
Increased age & some lung diseases have more of this small airway closure
Lung compliance
Factors that ↓compliance
1.
2.
3.
surface tension of fluid lining alveolar surface
elastic tissue in alveolar walls
expansion of lungs (stretched lungs are less compliant)
i.e, low levels in premature infants (respiratory distress syndrome)
higher or lower lung volumes,
higher expansion pressures,
venous congestion,
alveolar edema,
atelectasis & fibrosis
Factors that ↑compliance
1.
pulmonary surfactant secreted by type II alveolar cells
reduces surface tension of alveolar fluid mixture of phospholipid and
protein
with age
& emphysema secondary to alterations in elastic fibers
Compliance of whole system
1. The compliance of
lungs+thorax = ½
of lungs alone.
1. When lungs are expanded to
high volumes or compressed to
low volumes = limitations of
chest wall increase =
compliance of system is less
than 1/5
chest cage (A), lung (B),
combined chest lung cage(C)
SURFACE TENSION
Force exerted by fluid in alveoli to resist distension n.
In lungs = water tends to attract forcing air
out of alveoli tobronchi = alveoli tend to collapse
Lungs secrete and absorb fluid, leaving
a very thin film of fluid which causes.
That doesn’t happen because:
1.
Normally larger alveoli do not exist adjacent to small
alveoli = because they share the same septal walls.
2.
All alveoli are surrounded by fibrous tissue septa that act
as additional splints.
3.
Surfactant ↓ST = as alveolus becomes smaller surfactant
molecules are squeezed together ↑ their conc; = ↓ST
even more.
SURFACE TENSION OF DIFFERENT QUANTITATIVELY
1.
2.
3.
pure water, 72 dynes/cm;
fluids lining the alveoli but without surfactant, 50 dynes/cm;
fluids lining the alveoli and with normal amounts of surfactant 5
and 30 dynes/cm.
Surfactant Promotes Stability
2T
P
r
T
P
T
P
T
T
P
P
Alveolar Instability
T
T
P
P
P
P
How does filling the lungs with saline
alter lung compliance?
1. If lungs are filled with air, there is an interface
between the alveolar fluid and the air in the
V
alveoli.
2.Saline solution-filled lungs, there is no air-fluid
interface; therefore, the surface tension effect is
not present-only tissue elastic forces are
operative in the saline solution-filled lung.
Saline
Air
P
3. Transpleural pressures required to expand air-filled lungs are about
three times as great as those required to expand saline solution-filled
lungs.
4. Thus a much LARGER change in volume occurs for a smaller change
in pressure, meaning the compliance is increased.
Type II (granular pneumocytes)
are cuboidal, metabolically active
epithelial cells
→ thicker, contain numerous
lamellar inclusion bodies
→ make up 5% surface area
→ represent 60% epithelial
cells in alveoli
Surfactant
1. Lipids Consists
complex lipoprotein
1.
primarily of saturated dipalmitoylphosphatidylcholine (DPPC)
2.
Smaller fractions of unsaturated phosphatidylcholines (PCs)
Anionic phospholipids, i.e phospatidylglycerols (PGs)
Anionic lipids, , i.e palmitic acid (PA)
Neutral component , i.e , cholesterol
3.
4.
5.
2. Proteins 4 lung surfactant-specific proteins
SP-A and SP-D
1.
2.
3.
Larger proteins
Responsible for host defense mechanisms
Aid in transport and recycling of lung surfactant
SP-B and SP-C
1.
2.
Smaller proteins
Intensely hydrophobic Important to surface activity
3. Ca++
Functions of Surfactant
1.
Lowers surface tension of alveoli & lung
1.
2.
2.
Promotes stability of alveoli
1.
2.
3.
3.
300 million tiny alveoli have tendency to collapse
Surfactant reduces forces causing atelectasis
Assists lung parenchyma ‘interdependant’ support
Prevents transudation of fluid into alveoli
1.
2.
4.
Increases compliance of lung
Reduces work of breathing
Reduces surface hydrostatic pressure effects
Prevents surface tension forces from drawing fluid into alveoli from capillary;
LaPlace
Expansion of lungs at birth
Recently stated Functions of Surfactant
1.
2.
For xenobiotic metabolism, as well as enzyme activities
in host defense against invading organisms, and that it
contains antioxidant enzyme activity.that protect against
oxidant stress.
Soluble factors;1.that act locally on fibroblasts. regulatory mediators
in the coordination of normal lung development, and
repair of a damaged alveolar
2.several eicosanoids (PGI2, PGE2, TXB2, LTB4,
and LTC4), important in regulation of regional blood
flow and ventilation-perfusion matching.
SURFACTANT SYNTHESIS AND TURNOVER
1.
Following secretion, transform into a 3 D, latticelike
structure, tubular myelin.
2.
Tubular myelin is precursor to ST-lowering film of
dipalmitoylphosphatidylcholine(DPPC).
3.
Alveolar surfactant is in a constant state of flux; it turns
over every 5 to 10 hrs.
Quantity is adjusted with changes in alveolar volume,
occur rapidly;
NOTE;- can increase by 60% during exercise and quickly
return to pre-exercise levels with rest.
1.
SURFACTANT SYNTHESIS AND TURNOVER
1.
involve uptake and resecretion, degradation and
incorporation into new or complete removal from the
surfactant pool.
2.
Degraded by type II cells, alveolar macrophages,.
3.
Removal by mucociliary escalator and swallowing, transfer
across the alveolar endothelial-epithelial barrier into the
lymph and blood, or degradation and transfer of
breakdown products to other organs.
Work of
Breathing
1. Muscles perform work to cause inspiration (not expiration)
2. work of inspiration can be divided into 3 fractions:
1. 1.Compliance work or elastic work required to expand the lungs
against its elastic forces.
2. 2.Tissue resistance work. required to overcome the viscosity of the
lung and chest wall structures
3. 3.Airway resistance work. required to overcome airway resistance
3. Work energy required for respiration:
normal quiet respiration = 2 to 3% of the total work energy
( to 50 fold in exercise,  airway resistance).
RDS of newborn

Surfactant:

Synthesis begins in 28th week of gestation

Maximal amount of surfactant by 35 weeks.
Synthesis increased by cortisol and thyroxine.
 Synthesis is decreased by insulin
Normally begin to be secreted into the alveoli until between the 6-7
months of gestation,

1.
2.
premature babies have little or no surfactant when they are born
29
So What?
1.
Are these concepts important regarding lung disease?
Lung compliance changes ;
- in chronic obstructive lung diseases (COPD),
3.-↓ the ST in the alveoli 2-10-fold, which
normally plays a major role in preventing
alveolar collapse loss of surfactant is critical
in atelectasis(Lack of “Surfactant” as a
Cause of Lung Collapse)
2.
4.- near-drowning,
5. - infant respiratory distress syndrome, etc.
Compliance in Disease
Emphysema
Lung Volume
Normal
Fibrosis
Transpulmonary Pressure