1. Pulmonary Ventilation
Factors affecting
Pulmonary Ventilation
DR. QAZI IMTIAZ RASOOL

2. OBJECTIVES
Outline the various factors affecting airway resistance and correlate it to changes in pulmonary ventilation.
Describe the metabolism of surfactant, discuss its significance and relate its deficiency to clinical conditions.
Define compliance of the lung and chest wall, illustrate and discuss the compliance curve and describe the effect of surfactant on it.
Discuss work of breathing and relate it to clinical conditions.

3. Poiseuille’s Law for Pressure.
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.
Hagen–Poiseuille Equation[edit source | editbeta]
In fluid dynamics, the Hagen–Poiseuille equation is a physical law that gives the pressure drop in a fluid flowing through a long cylindrical pipe. The assumptions of the equation are that the flow is laminar viscous and incompressible and the flow is through a constant circular cross-section that is substantially longer than its diameter. The equation is also known as the Hagen–Poiseuille law, Poiseuille law and Poiseuille equation.
Where:
= Pressure difference between the ends of the pipe
= Length of pipe
= the dynamic viscosity
= the volumetric flow rate (Q is usually used in fluid dynamics, however in respiratory physiology it denotes cardiac output)
= the radius of the pipe
Dividing both sides by and given the above definition shows:-
While the assumptions of the Hagen–Poiseuille equation are not strictly true of the respiratory tract it serves to show that, because of the fourth power, relatively small changes in the radius of the airways causes large changes in airway resistance.
An individual small airway has much greater resistance than a large airway, however there are many more small airways than large ones. Therefore resistance is greatest at the bronchi of intermediate size, in between the fourth and eighth bifurcation.[1]
Laminar flow versus Turbulent flow[edit source | editbeta]
Where air is flowing in a laminar manner it has less resistance than when it is flowing in a turbulent manner. If flow becomes turbulent, and the pressure difference is increased to maintain flow, this response itself increases resistance. This means that a large increase in pressure difference is required to maintain flow if it becomes turbulent.
Whether flow is laminar or turbulent is complicated, however generally flow within a pipe will be laminar as long as the Reynolds number is less than 2300.[2]
where:
is the Reynolds number
is the diameter of the pipe.
is the mean velocity.
is the dynamic viscosity.
is the density.
This shows that larger airways are more prone to turbulent flow than smaller airways. In cases of upper airway obstruction the development of turbulent flow is a very important mechanism of increased airway resistance, this can be treated by administering Heliox which is much less dense than air and consequently more conductive to laminar flow.

4. Airway Resistance 4. Resistance is usually insignificant because of
(Raw) is defined as the pressure difference between the mouth and the alveoli divided by the flow rate. (flow changes inversely with resistance)
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
Resistance is usually insignificant because of
Large airway diameters in the first part of the conducting zone
Airway resistance (Raw) is defined as the pressure difference between the mouth and the alveoli divided by the flow rate. (flow changes inversely with resistance)
Flow of air depends on the pressure gradient (atmospheric, Pa, and intra-alveolar, Pi) and the airway resistance, R
F = (Pa - Pi)/R
P is the pressure gradient between the atmosphere and the alveoli (2 mm Hg or less during normal quiet breathing)
4. Resistance is usually insignificant because of
Large airway diameters in the first part of the conducting zone

5. 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
Less than 20% drop at airways less than 2mm
Paradox secondary to prodigious number of small airways in parallel
Rtotal=1/R1+1/R2+1/R3)
Air velocity becomes low, diffusion takes over
major site of airway resistance is along the bronchial tree is the large bronchi. The smallest airways contribute very little to the overall total resistance of the bronchial tree. This is due to
Air flow velocity decreases substantially as the effective cross sectional area increases (i.e. flow becomes laminar)
Airway generation exists in parallel rather than in series. (Rtotal=1/R1+1/R2+1/R3)

6. Factors Determining Airway Resistance
Lung Volume
Linear relationship between lung volumes & conductance of airway resistance
As lung volume is reduced - airway resistance increases
Bronchial Smooth Muscle
Contraction of airways increases resistance
Bronchoconstriction caused by PSN, acetylcholine, low pCO2, direct stimulation, histamine, environmental, cold
Density & Viscosity Of Inspired Gas
Increased resistance to flow with elevated gas density
Changes in density rather than viscosity have more influence on resistance
Resistance and Disease
Asthma: Constriction of small airways, excess mucus, and histamine- induced edema
Bronchitis: Long term inflammatory response causing thickened walls and overproduction of mucous
Emphysema: Collapse of smaller airways and breakdown of alveolar wall

7. APPLIED Normally RAW is ∼1.5 ( 0.6 - 2.3). cm H2O/(L/s)
RAW respiratory disease can > 10 cm H2O/(L/s).

8. 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 (0.08/cm H2O)
2. Elastance as the change in pressure per unit change in volume and it is the reciprocal of compliance =∆P/∆V
Ease with which volume can be changed (expanded)
Distensiblity: how easily the lungs can be distended (stretched)

9. What keeps the alveoli (lungs) expanded are:
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)

10. Elastic Forces of the Lung
Elastic Lung Tissue
Elastin & Collagen fibers of lung parenchyma1/3rd
Natural state of these fibers is contracted coils
Elastic force generated by the return to this coiled state after being stretched and elongated
The recoil force assists to deflate lungs
Surface Air-fluid Interface
2/3 rd of total elastic force in lung is due to H2O
Complex synergy between air & fluid holds alveoli open
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 collapsing

11. Method of P-V Curve Measurement
Esophageal
Balloon
In esophagus
adjacent to
pleura t P

12. 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.
Curves during inflation & deflation are different
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

13. Pressure-Volume Curve
Expiration
Inspiration
Hysteresis
Non-linear curve
Volume
Curves during inflation & deflation are different
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

15. Lung compliance Factors that ↓compliance
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
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 1
lung volume , expansion pressure, venous congestion, edema, atelectasis, fibrosis, age & emphysema
00 x more distensible than a balloon.

16. Compliance of whole system
The compliance of lungs+thorax = ½
of lungs alone.
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)

17. 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:
Normally larger alveoli do not exist adjacent to small alveoli = because they share the same septal walls.
All alveoli are surrounded by fibrous tissue septa that act as additional splints.
Surfactant ↓ST = as alveolus becomes smaller surfactant molecules are squeezed together ↑ their conc; = ↓ST even more.
SURFACE TENSION Force exerted by fluid in alveoli to resist distension n.
acts in the plane of the air-liquid boundary to shrink or minimize the liquid-air interface

18. SURFACE TENSION OF DIFFERENT QUANTITATIVELY
1. 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.

19. Surfactant Promotes Stability

20. Alveolar Instability P T P

21. 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
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.
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. P V
Air
Saline

22. 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
The “space” between the endothelium and the type-1 pneumocyte, is the blood air interface
The alveolar surface is lined by two distinct populations of epithelial cells .
Type I alveolar epithelial cells are thin, flattened cells that cover approximately 95% of the alveolar surface; they are thought to be relatively quiescent metabolically and form the epithelial surface of the gas diffusion barrier

23. Surfactant complex lipoprotein
1. Lipids Consists
primarily of saturated dipalmitoylphosphatidylcholine (DPPC)
Smaller fractions of unsaturated phosphatidylcholines (PCs)
Anionic phospholipids, i.e phospatidylglycerols (PGs)
Anionic lipids, , i.e palmitic acid (PA)
Neutral component , i.e , cholesterol
2. Proteins 4 lung surfactant-specific proteins
SP-A and SP-D
Larger proteins
Responsible for host defense mechanisms
Aid in transport and recycling of lung surfactant
SP-B and SP-C
Smaller proteins
Intensely hydrophobic Important to surface activity
3. Ca++
Phospholipid produced by alveolar type II cells.
Lowers surface tension.
Reduces attractive forces of hydrogen bonding by becoming interspersed between H20 molecules.
As alveoli radius decreases, surfactant’s ability to lower surface tension increases
Causes of decreased surfactant in the fetal lungs
Prematurity
(gestational age <36 weeks)
Maternal diabetes:
fetal hyperglycemia  ↑insulin release  ↓surfactant synthesis
Cesarean section:
no stress on baby  no release of cortisol.
Surfactant is stored in cytoplasmic lamellar bodies that fuse with the cell membrane to release surfactant components into the alveolar space by exocytosis.
Surfactant secretion is regulated by soluble mediators, such as glucocorticoids and b-adrenergic agonists, as well as by intracellular second messenger signals generated by mechanical strain in the type II cell.

24. Functions of Surfactant
Lowers surface tension of alveoli & lung
Increases compliance of lung
Reduces work of breathing
Promotes stability of alveoli
300 million tiny alveoli have tendency to collapse
Surfactant reduces forces causing atelectasis
Assists lung parenchyma ‘interdependant’ support
Prevents transudation of fluid into alveoli
Reduces surface hydrostatic pressure effects
Prevents surface tension forces from drawing fluid into alveoli from capillary; LaPlace
Expansion of lungs at birth

25. Recently stated Functions of Surfactant
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.

26. SURFACTANT SYNTHESIS AND TURNOVER
Following secretion, transform into a 3 D, latticelike structure, tubular myelin.
Tubular myelin is precursor to ST-lowering film of dipalmitoylphosphatidylcholine(DPPC).
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.

27. SURFACTANT SYNTHESIS AND TURNOVER
involve uptake and resecretion, degradation and incorporation into new or complete removal from the surfactant pool.
Degraded by type II cells, alveolar macrophages,.
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.

28. Work of Breathing
Muscles perform work to cause inspiration (not expiration)
work of inspiration can be divided into 3 fractions:
1.Compliance work or elastic work required to expand the lungs against its elastic forces.
2.Tissue resistance work. required to overcome the viscosity of the lung and chest wall structures
3.Airway resistance work. required to overcome airway resistance
Work energy required for respiration:
normal quiet respiration = 2 to 3% of the total work energy
( to 50 fold in exercise,  airway resistance).

29. 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,
premature babies have little or no surfactant when they are born
Women who must deliver prematurely receive glucocorticoids to increase fetal surfactant synthesis hence reducing the potential to develop RDS.
Surfactant (lecithin) decreases surface tension, which keeps the alveoli open during expiration.

30. So What? 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)
4.- near-drowning,
5. - infant respiratory distress syndrome, etc.

31. Compliance in Disease Emphysema Normal Lung Volume Fibrosis
Transpulmonary Pressure