LUNG MECHANICS

Static (Relaxation) Pressure Volume Curves

(Interaction of Lung & Chest Wall Elastic Recoil Forces)
[1] At TLC:
Chest wall is stretched slightly beyond its equilibrium position and wants to collapse (+ve recoil force).
Lung is also stretched and wants to collapse (+ve recoil force).
Lung and chest wall exert a large net inward force. As you hold your lungs at TLC, your respiratory
muscles must actively counter this large inward force generated by the lung and chest wall.

[2] At 80% TLC:

Chest wall force vector has a magnitude of 0, which is seen on the graph as the chest wall line crossing the
0 pressure axis. Chest wall is at its equilibrium position.
Lung is stretched and wants to collapse.
Net inward force is generated by the lung only. When you hold your lungs at this point, your respiratory
muscles must actively counter this inward force.

[3] At FRC:
Chest wall is compressed and wants to expand (-ve recoil force)
Lung wants to collapse. Lung and chest wall exert equal and opposite Forces.
Net force = 0, which is seen as Lung + Chest wall line crossing the 0 pressure axis. No respiratory muscle
activity is required to hold your lung and chest wall at this position.

[4] At RV:
Chest wall is highly compressed and wants to spring out forcefully.
Lung still wants to collapse. But since the lung volume is small the collapsing force (ELR) is of
smaller magnitude.
At this lowest achievable lung volume respiratory muscles are required to counteract the
net outward force generated by the lung and chest wall.

Also called static compliance curves. Though the X-axis is marked PTM you should think of it as Recoil
Pressure. Pictures show Transmural Pressure Vs. Volume for the Isolated Lung / Isolated Chest Wall &
Combined System, under static conditions (Pressures were measured at each lung volume with the glottis
open & no air movement occuring). Illustrates relationship between lung (alveolar) elastic recoil force
and chest wall elastic recoil force. For the chest wall, the transmural pressure gradient = intrapleural
pressure atmospheric pressure.

Chest wall and lung (alveoli) have elastic recoil forces and will resist a change in volume from their
resting positions.
The resting position for the isolated chest wall is at a volume that is 80% TLC (Point at which the
chest wall line crosses the 0 pressure axis). At thoracic volumes below 80% of TLC, the chest wall
elastic recoil is outward (-ve). At thoracic volumes above 80% of TLC, the recoil is inward (+ve).
The resting position for the isolated lung is near 0% TLC (much below RV). Point at which the
lung line crosses the 0 pressure axis. The combined system will never reach this point. At this point
there is virtually no air in the alveoli. To expand the lung above this volume a +ve transmural force is
required.
The resting position for the combined system = Volume at FRC. The outward chest wall recoil
force and inward alveolar recoil force are equal and opposite in direction. Point at which the combined
system line crosses the 0 pressure axis. The equal and opposite forces are maintained by the ve
intrapleural pressure (-5 cmH2O). FRC is the volume of the lungs at the end of a normal tidal
expiration, when no respiratory muscles are actively contracting. At lung volumes above FRC: the
total system recoil pressure becomes positive because of two factors: the increased inward elastic
recoil of the lung and the decreased outward elastic recoil of the chest wall. In fact, at high lung
volumes the recoil pressure of the chest wall is also positive. At lung volumes below the FRC: the
recoil pressure is negative because the outward recoil of the chest wall is greater than the reduced
inward recoil of the lungs.
The combined system line is the algebric sum of the chest wall and lung curves.
The point at which the curve crosses the 0 pressure line is the resting volume of that structure.
To e or e the volume of the lung / chest wall / combined system from their resting volumes a
pressure (force) is required. This is called the transmural pressure (PTM) (Pressure Inside Pressure Outside). It is the pressure across the wall of an enclosed structure. +ve PTM is an expanding
force (Pressure Inside > Pressure Outside) while ve PTM is a collapsing force (Pressure Outside >
Pressure Inside). Resting (Unstressed) position = Volume at which PTM = 0.

Transpulmonary Pressure (PTP) = Distending Pressure of the Lung. Think of PTP as the distending
pressure inside a balloon with the outside pressure zero (atmospheric). As you PTP you blow up the balloon.

PTP = PA PIP
(Inside Pressure Outside Pressure). Note that a ve intrapleural pressure will act as a distending force thus
ing PTP. A +ve intrapleural pressure will act as a collapsing force thus ing PTP. PIP is always < PA. Alveolar
Pressure will inturn depend on:

PA = Pelas + PIP
Alveolar Pressure = Elastic Lung (Alveolar) Recoil Force + Intrapleural Pressure
Elastic lung (alveolar) recoil is directly proportional to lung volume. If the lung (alveolar) volume es
ELR will e. If it es ELR will also e. During Normal quiet breathing alveoli expand because of a
more negative intrapleural pressure (PTP) and alveoli return to their previous pre-inspiratory size because of
the ed elastic lung (alveolar) recoil (secondary to the ed alveolar volume). Sequence: PIP (PTP) ed
alveolar size ELR alveolar size. ELR should rightly be called EL(A)R.
Important Note: When you change PTP you are also changing ELR (because of the change in volume). PTP
and ELR are equal in signs & magnitude but opposite in direction (therefore in some places they are used
interchangeably). A +ve Recoil force will collapse the structure while a ve recoil force will expand the
structure. Compliance Stiffness (or) Recoil Force (are opposites forces).

At the end of expiration, the muscles of respiration are relaxed. The inward elastic recoil of the lung is balanced by the
outward elastic recoil of the chest wall. Intrapleural pressure is -5 cm H2O; alveolar pressure is 0. The transmural
pressure gradient across the alveolus is +5. Since alveolar pressure is equal to atmospheric pressure, no airflow occurs.
Simple Pneumothorax: The integrity of the lungchest wall system is disturbed by a penetrating knife wound. Air
moves in through the wound until PIP equalizes with Patm. PTP gradient is abolished. At this point nothing is tending to hold
the alveoli open and their elastic recoil is causing them to collapse. Similarly, the chest wall tends to expand because its
outward recoil is no longer opposed by the inward recoil of the lung.
Events Involved in a Normal Tidal Breath
Inspiration
[1] Diaphragm (and) external intercostals contract
[2] Chest wall expands and thoracic volume es
[3] PIP becomes more ve
[4] PTP es
[5] Alveoli expand (according to their individual compliance curves). This es ELR. Alveolar (lung) recoil force is directly
proportional to alveolar (lung) volume.
[6] Alveolar volume es. PA falls below Patm (i.e PA becomes ve), thus establishing a pressure gradient for airflow
[7] Air flows into the alveoli restoring PA = 0
Expiration (Passive)
[1] Inspiratory muscles relax (passive process)
[2] Thoracic volume decreases
[3] PIP becomes less ve
[4] PTP es
[5] ed PTP allows the ed ELR to return the alveoli to their preinspiratory volumes
[6] Alveolar volume es & the alveolar gases are compressed. PA rises above Patm(i.e PA becomes +ve), thus establishing
a pressure gradient for airflow
[7] Air flows out of the alveoli restoring PA = 0

Breathing Cycle (Eupnia)

Important: The balloon can be blown either by ing outside pressure (making PIP more ve) or by ing
inside pressure (making PA more +ve).
Figure: The dashed line predicts the changes in PIP necessary to overcome the elastic recoil of the alveoli
(elastic work). The solid line is a more accurate representation of PIP because it also includes the additional
pressure work (resistive work) that must be done to overcome the resistance to airflow.

Supine Subject = Abdominal contents passively elevate the diaphragm es the outward elastic recoil of
the chest wall chest wall elastic recoil curve shifted to the right. Because the respiratory system
curve is the sum of the lung and chest wall curves, it is also shifted to the right. Elastic lung recoil curve
remains unchanged. The lung volume at which the outward recoil of the chest wall is equal to the inward
recoil of the lung is much lower in the supine subject (i.e FRC is decreased).

Dynamic compliance = Change in the volume of the lungs divided by the change in the alveolar-distending
pressure during the course of a breath.
Normal: DC/SC = 1 (i.e., DC = SC, even at high RRs).
Patients with obstructive diseases of the small airways:
DC/SC es dramatically as RR is ed.
Changes in dynamic compliance is because of changes in airways resistance. In a patient with smallairways disease, many alveoli may be supplied by airways with higher resistance to airflow than
normal. These alveoli are referred to as slow alveoli (Fill & empty more slowly because of ed
resistance). Slow alveoli = poorly ventilated alveoli.
As the patient increases the breathing frequency, the slowest alveoli will not have enough time to fill
and will contribute nothing to the dynamic compliance.
This situation also leads to a redistribution of alveolar air after the inflating pressure has ceased. The
more distended alveoli have ed ELR, and because they are joined by a common airway, some air will
flow into the slower alveoli.
Figure: Gas is slow to enter it, and it therefore continues to fill after the rest of the lung has stopped
filling.
FORCED VITAL CAPACITY (FVC)
[1] Normal FEV1/FVC 0.8 (atleast 80% of FVC is expired in the first second)
FEV1/FVC (Obstructive Disease) < 0.8
[2] FEF25-75% (OR) MMFR = Forced Expiratory Flow at 25% - 75% Vital Capacity (MMFR is the old name)
Slope of line between 25% and 75% of FVC
Normal = Steep / OD = Less Steep
Both [1] and [2] convey the same info.
FVC test = Maximal inspiration to the TLC followed by a maximal forced expiratory effort, blowing as much
air as possible out of the lungs leaving only RV behind. The part of the curve most sensitive to changes in
expiratory airways resistance is the first second of expiration. The volume of air expired in the first second of
expiration (FEV1, or Forced Expiratory Volume in 1 second) when expressed as a ratio with the total amount
of air expired during the FVC (FEV1/FVC) = good index of expiratory airway resistance.

Flow Volume Curves: Flow rates are plotted against lung volume for varying expiratory efforts. Often used
clinically. At high lung volumes, the airflow rate is effort-dependent, which can be seen in the left-hand portion of the
curves. At low lung volumes, however, the expiratory efforts of different initial intensities all merge into the same effortindependent curve, as seen in the right-hand portion of the curve. This difference is because intrapleural pressures high
enough to cause dynamic compression are necessary to attain very low lung volumes, no matter what the initial
expiratory effort. Also, at low lung volumes there is ELR (less traction on the airways).

[1] Maximal Expiratory flow-volume curves: help to distinguish between ODs (Obstruct airflow) and RDs (restrict
lung expansion). Both obstruction and restriction decrease the maximal flow rate (PEF) that the patient can attain (but
this e occurs for different reasons).
RD

OD

PEF is because of TLC (and therefore VC)

Elastic Lung Recoil
Effort-independent part of the curve is similar to that obtained from a person with normal lungs.
FEV1/FVC = N (or) ( Lung Volume & ELR = they get rid of the smaller volume faster).
(Asthma / Bronchitis / Emphysema)
FEV1/FVC ed
lung volumes = beneficial because the high volumes e ELR
The RV may be greatly ed if airway closure occurs at relatively high lung volumes.
Effort-independent portion of the curve is depressed inward (Expiratory coving (or) Scooped out appearance):
flow rates are low for any relative volume.

[2] Dx. Of Fixed (or) Variable / Intra (or) Extra Thoracic Upper Airway Obstruction:
Flow-volume curves are very useful in assessing obstruction of the upper airways and the trachea. Flowvolume loops can help distinguish between fixed obstructions (those not affected by the inspiratory or
expiratory effort) and variable obstructions (changes in the transmural pressure gradient caused by the
inspiratory or expiratory effort result in changes in the cross-sectional area of the obstruction).
Paw = airway pressure
Patm = atmospheric pressure
Ppl = intrapleural pressure
CSA = cross-sectional area (airway diameter)
PEF = peak expiratory flow

Fixed lesion means pleural pressure does not affect the degree of obstruction. Both the expiratory and
inspiratory flow-volume curves are truncated, with equivalent decrease in peak expiratory and peak
inspiratory flows. The flow-volume loop is unable to distinguish between a fixed extrathoracic and a fixed
intrathoracic obstruction (Use bronchoscopy). Causes: Foreign bodies / Scarring (airway too stiff to be
affected by the transmural pressure gradient).

During a forced expiration, the CSA of a variable extrathoracic obstruction increases as the
pressure inside the airway increases. The expiratory flow-volume curve is therefore normal.
During a forced inspiration, the pressure inside the upper airway decreases below atmospheric
pressure, and (unless the radius of the upper airway is maintained by reflex contraction of the
pharyngeal muscles) the CSA of the upper airway will decrease. Inspiratory flow-volume curve is
truncated.
Causes: Tumors / fat deposits / weakened pharyngeal muscles (as in obstructive sleep apnea) /
paralyzed vocal cords / enlarged lymph nodes / inflammation.

During a forced expiration, positive intrapleural pressure decreases the transmural pressure
gradient across a variable intrathoracic tracheal obstruction, decreasing its CSA and
decreasing the peak expiratory flow (PEF).
During a forced inspiration, large negative intrapleural pressures are generated, the transmural
pressure gradient across the variable intrathoracic obstruction increases and its CSA increases.
Thus, the inspiratory flow-volume curve is normal.
Causes: Most commonly caused by tumors.
Remember: E cuts off I (Inspiratory PEF truncated); I cuts off E (Expiratory PEF truncated)

A variable intrathoracic lesion is characterized by expiratory limitation of airflow and a plateau on the expiratory portion
of the flow-volume curve, whereas a variable extrathoracic lesion demonstrates inspiratory limitation of airflow and a
plateau on the inspiratory portion of the flow-volume curve.
Conducting zone: Contain no alveoli and thus are anatomically incapable of gas exchange (anatomic dead space).
Consists of trachea / bronchi / bronchioles / Terminal bronchioles. By definition, airways with no cartilage are termed
bronchioles.
Respiratory zone: acinus (portion of lung supplied by a respiratory bronchiole). Includes respiratory bronchioles
(Transitional zone) / alveolar ducts / alveolar sacs. Gas exchange.
Positive-pressure ventilation: positive pressure is exerted on the opening to distend the elastic wall and fill it with air.
Negative-pressure breathing: negative pressure applied to the outside of the lungs to cause their expansion.

Alveoli do not hang from the airways like a bunch of grapes and they are not spheres. They are mechanically
interdependent polygons with flat walls shared by adjacent alveoli (and airways). Both surfactant and mechanical
interdependence of the alveoli help stabilize the alveoli and oppose alveolar collapse (atelectasis). Also the pressure
at the pleural surface is transmitted through the alveolar walls (alveolar septa) to more centrally located alveoli and
small airways (intermingled with alveoli) in negative pressure breathing (peripheral alveoli more distended). In positive
pressure ventilation the peripheral alveoli might be more compressed than those located centrally (central alveoli more
distended).
During normal quiet breathing (Eupnea), diaphragm descends 1 to 2 cm into the abdominal cavity (upto 10 cm with
deep inspiration). Expiration is passive during eupnea. As the inspiratory muscles relax, the increased elastic recoil of the
distended alveoli is sufficient to decrease the alveolar volume and raise alveolar pressure above atmospheric pressure.
During Eupnea, the expiratory phase (like diastole) is longer than the inspiratory phase (like systole). The intrapleural
pressure can be estimated by having a subject swallow a balloon into the intrathoracic portion of the esophagus.
Normal Inspiration: Diaphragm / EIC. Exercise: + Scalene / SCM
Normal Expiration: Passive. Exercise: Abd (rectus abdominis / internal & external oblique / transversus abdominis) /
IIC
Work of Breathing (WOB) = Pressure Change Volume Change. With ed work the O2 cost es. WOB is manifested
clinically as Dyspnea. Volume change = Volume of air moved in and out of the lung. Pressure Change = PTP needed to
overcome the elastic work & resistive work:
[1] Elastic Work = Work done to overcome the

Elastic recoil of the chest wall (ed chest wall compliance in kyphoscoliosis / aging / obesity). Obese patients
have increased inward chest wall elastic recoil.

Elastic recoil of the alveoli (Restrictive Diseases Pulmonary Fibrosis)

Surface tension of the alveoli (RDS)

[2] Resistive Work = Work done to overcome resistance to airflow.

ODs (asthma / bronchitis / emphysema) / upper airway obstruction / FB aspiration / dynamic compression (with
forced expiration).

Emphysema = destruction of the alveolar septa (elastic tissue support of the small airways) allows dynamic
compression to occur unopposed.

The slope between two points on a pressure-volume curve is known as the compliance.Compliance = volume /
pressure. Lungs with high compliance have a steep slope on their pressure-volume curves (small change in
distending pressure will cause a large change in volume).
Lung compliance is volume-dependent (greater at low lung volumes and lower at high lung volumes). At high
lung volumes the distensible components of alveolar walls have already been stretched, and large increases in
transpulmonary pressure yield only small increases in volume.
Compliance is the inverse of elasticity, or elastic recoil (Elastic Lung Recoil is Contributed by lung parenchyma
(Elastin / Collagen) + Surface Tension Forces). Compliance denotes the ease with which something can be
stretched; elasticity refers to the tendency for something to oppose stretch, as well as to its ability to return to
its original configuration after the stretching force is removed.
Both lungs together are more compliant than either one alone.
The curve obtained is the same whether the lungs are inflated with positive pressure (by forcing air into the
trachea) or with negative pressure (from outside). How the transpulmonary pressure is generated is not
important.
Hysteresis = [1] Some pressure is required to break the inter-molecular forces created by surface tension, [2]
some alveoli or small airways may open on inspiration (recruitment).
Decreased compliance: for any increase in transpulmonary pressure there is less of an increase in lung
volume. Curve is shifted to the right. Examples: Fibrosis ( Connective Tissue es alveolar elastic recoil) /
pulmn. Edema (vascular congestion) / atelectasis / presence of air, excess fluid, or blood in the intrapleural
space / ed surfactant / Surgical removal of 1 lobe.
Increased Compliance: Emphysema increases the compliance of the lungs because it destroys alveolar septal
tissue that normally opposes lung expansion.
Decreased chest wall compliance in obesity (moving the diaphragm downward and the rib cage up and out is
much more difficult) and kyphoscoliosis (decreased mobility of the rib cage).
WOB: In people with decreased compliance of the lungs WOB es (must generate greater transpulmonary
pressures to breathe in the same volume of air).
The total compliance at FRC is about 0.1 L/cm H2O. The compliance of the lungs is about 0.2 L/cm H2O; that of
the chest wall is also about 0.2 L/cm H2O. Total compliance is less than either one alone (Balloon inside another
balloon analogy).
Alveoli are more compliant and have less elastic recoil force at low (lung) volumes. Alveoli are less compliant and
have more elastic recoil force at high (lung) volumes.

Surface Tension Forces:

Occur at any gas-liquid interface. Generated by the cohesive forces between the molecules of the liquid. It
causes a liquid to shrink to form the smallest possible surface area.

In a saline filled lung model (No surface tension forces involved), elastic recoil is due only to the elastic recoil
of the lung parenchyma itself (and therefore is more compliant) and there is no hysteresis.

The lung is composed of interconnected alveoli of different sizes. If the surface tension was constant with no
area-dependence it would be inherently unstable, with a tendency for smaller alveoli to collapse into larger
ones. Collapse is not good because collapsed alveoli require very great distending pressures to re-open, because
of the cohesive forces at the liquid-liquid interface of collapsed alveoli.

2 factors e stability (and therefore prevent collapse) [1] pulmonary surfactant, [2] mechanical
interdependence of alveoli.

Area dependence: Surfactant lowers even further the surface tension of smaller alveoli, equalizing the pressure
inside alveoli of different sizes. Smaller alveoli have lower surface tensions (as the alveoli shrink, the effective
concentration of surfactant es) as r falls so does T. With a lack of surfactant tendency toward spontaneous
collapse of smaller alveoli es.

Figure: If the surface tension is the same in both alveoli, then the smaller alveolus will have a higher pressure
and will empty into the larger alveolus.

WOB: Pulmonary surfactant es surface tension ed elastic lung recoil means ed compliance es WOB
(especially inspiration). Lack of surfactant es WOB.

Surfactant also indirectly stabilizes the small airways.

Treatment of ARDS & IRDS:

PEEP - Keeps alveolar pressure above atmospheric pressure during expiration. This opposes the increased elastic
recoil of the alveoli and the tendency for spontaneous atelectasis.

Exogenous pulmonary surfactant directly into the airway of neonates with infant respiratory distress
syndrome.
Airway Resistance:

30% of the total resistance to airflow is located in the upper

airways, upto the Larynx. The muscles of the oropharynx contract
during normal inspirations, which dilates and stabilizes the upper airway.

Resistance is higher when one breathes through the nose than

through the mouth / at low lung volumes / with forced expirations.

The vocal cords open slightly during normal inspirations and

close slightly during expirations. During deep inspirations, they open
widely.

Resistances of small airways add as reciprocals (aranged in

parallel) extremely low resistance to airflow in the periphery of the
lung.

Highest resistances are found more centrally with peak airway

resistance occurring in the 5th to 7th generation of airways (mediumsized bronchi).

Diseases of the central airways have a significant impact on total resistance in the lung and are detected early, whereas diseases of the small
airways show up late on testing (this region is therefore called the silent zones of the lungs).

Control of Bronchial Smooth Muscle Tone

Constriction: Parasym. stimulation / Ach / Histamine /

Leukotrienes / Thromboxane A2 / Serotonin / a-Adrenergic

agonists / Decreased PCO2 in small airways / Chemical irritants
Dilatation: Sympathetic stimulation (b2 receptors) / Circulating b2 agonists / NO / Increased PCO2 in small airways /
Decreased PO2 in small airways
(Underlined = Help balance ventilation and perfusion)

Airways resistance es with ing lung volume. 2 Reasons. Both mainly involve the small airways which
have little or no cartilaginous support.
[1] PIP es and therefore PTP es Airway distends
[2] The small airways traveling through the lung form attachments to the walls of alveoli. Alveoli Expand
ed Elastic recoil in alveolar wall (alveolar septa) Exerts radial traction on airway pulling it open. Elastic
Lung Recoil (alveolar septal traction) is an important force opposing dynamic airway compression.
Emphysema = (Picture on the right) Alveolar septa destroyed (ed recoil force & ed compliance) less
traction on airways airway resistance es.
If the reciprocal of resistance (conductance) is plotted against lung volume, an approximately linear
relationship is obtained.

Dynamic Airway Compression:

All pressures are in cm H2O; Intrapleural pressure = +25; Alveolar elastic recoil pressure = +10; Alveolar pressure =
+35; Blue arrow = Equal Pressure Point

The muscles of expiration are generating a +ve intrapleural pressure of +25. Pressure in the alveolus is
higher than intrapleural pressure because of the alveolar elastic recoil pressure of +10, which together with
intrapleural pressure, gives an alveolar pressure of +35.
The alveolar elastic recoil pressure will e at lower lung volumes.
The airways are not uniformly rigid and the smallest airways, which have no cartilaginous support and
rely on the traction of alveolar septa to help keep them open will collapse.
ed resistance during a forced expiration is called dynamic compression of airways.
During a maximal forced expiration, as the expiratory effort is ed to attain a lower and lower lung volume,
intrapleural pressure is getting more and more +ve (and more and more dynamic compression will occur) & as
lung volume es, there will be less alveolar elastic recoil pressure and the difference between PA and PIP (PTP)
will e.
At any instant during a forced expiration, there is a point along the airways where the pressure inside the airway
is just equal to the pressure outside the airway. At that point the transmural pressure gradient is 0 (arrows).
Above that point, the transmural pressure gradient is ve (the pressure outside the airway is greater than the
pressure inside it), and the airway will collapse (if cartilaginous support or alveolar septal traction is insufficient
to keep it open).
As the forced expiratory effort continues, the equal pressure point (EPP) is likely to move down the airway
from larger to smaller airways. This movement happens because: [1] as effort es, PIP es and [2] as lung
volume es, alveolar elastic recoil pressure es. As the equal pressure point moves down the airway, dynamic
compression es and the airways ultimately begin to collapse.
This airways closure can be demonstrated only at especially low lung volumes in healthy subjects, but the
closing volume may occur at higher lung volumes in patients with emphysema.
During a forced expiration, when intrapleural pressure becomes positive and dynamic compression is occuring,
the effective driving pressure for airflow from the lung is PA PIP (which is equal to the alveolar elastic recoil
pressure), instead of PA Patm.

Repeated expiratory maneuvers with increasing effort (= Increasing PIP). Measure airflow rate.
PIP plotted against airflow rate for several expiratory maneuvers as the lung passes through a
particular volume. Therefore each curve is not a continuous line. Each curve is constructed from
individual data points.
Each Curve = Lung Volume Constant = Therefore ELR (Elastic Lung Recoil) remains constant.
B and C = demonstrates dynamic compression and supports the equal pressure point (EPP)
hypothesis. With increasing expiratory effort, airflow increases up to a point. Beyond that point,
generating more positive intrapleural pressure does not increase airflow: It is effort-independent.
Airflow has become independent of effort because of greater dynamic compression with more positive
intrapleural pressures. The equal pressure point has moved to compressible small airways and
is fixed there. At even lower lung volumes (C), at which there is less alveolar elastic recoil, EPP occurs
with lower maximal airflow rates. The driving pressure for airflow becomes independent of expiratory
muscle effort because increasing the intrapleural pressure increases the alveolar pressure by the
same amount. Only the alveolar elastic recoil, which is constant at a given lung volume, drives air out
of the lung.
A = At high lung volumes airflow increases steadily with increasing effort. It is entirely effortdependent because alveolar elastic recoil pressure is high, which increases both the alveolar septal
traction on small airways and the pressure gradient for airflow.

Transitional flow is a mixture of laminar and turbulent flow. This type of flow
often occurs at branch points or points distal to partial obstructions. Turbulent
flow tends to occur if airflow velocity is high, gas density is high, the tube radius
is large. True laminar flow probably occurs only in the smallest airways, where
the linear velocity of airflow is extremely low. Concentrically arranged cylinders of
air flowing at different rates (telescopic flow).

Work = Pressure Volume

During Inspiration:
Total work done = 0ABCD0
Elastic work = 0ECD0
Resistive work = ABCEA (hatched area). The higher the airway resistance or the inspiratory flow rate, the more
negative (rightward) would be the intrapleural pressure excursion between A and C and the larger the area.
During Expiration:
Resistive work = AECFA (this falls within 0AECD0, and thus this work can be accomplished by the energy stored in the
expanded elastic structures and released during a passive expiration).
0AFCD0 = work dissipated as heat.
The higher the breathing rate, the faster the flow rates and the larger the resistive work area ABCEA. On the other hand,
the larger the tidal volume, the larger the elastic work area 0AECD0. Patients who have a reduced compliance (stiff
lungs) tend to take small rapid breaths, whereas patients with severe airway obstruction breathe slowly. These patterns
tend to reduce the work done on the lungs. The O2 cost of quiet breathing is less than 5% of the total resting O2
consumption. Can go up to 30% in patients with obstructive lung disease (the O2 cost of breathing may limit their
exercise ability). Mechanical Ventilation (in acute respiratory failure) - Fatigued respiratory muscles are allowed to
recover, and the large amount of blood flow (& O2) required by overworking respiratory muscles can be shifted to perfuse
other organs.
Dynamic Compression:
[1] Forced expiration at the same lung volume: PA = (+10) + (+25) = +35. PA > PIP. Elastic lung recoil lung volume.
With forced expiration PIP & PA will e but ELR depends only on lung volume.
[2] Forced expiration in emphysema:
Less elastic recoil (more compliant lung) airway / alveolar pressure are lower.
Dynamic compression: airway collapse ed resistance to airflow airflow becomes effort independent.
As lung volume es during expiration ELR es and PIP es (ed effort) EPP moves down from larger to smaller more
compressible airways. Closing volume: lung volume at which airway closure begins to occur. Is low in normal subjects. Is
high in emphysema (airway closure happens even at high lung volumes).
PTP depends on 2 opposing forces:[1] PIP; [2] PA (which inturn depends on ELR & PIP)

ELR = important force opposing dynamic compression (because of traction on airway by alveolar septa)
P = pressure gradient for airflow (Q=P/R)
During normal expiration: P = PA Patm
During forced expiration with dynamic compression: P = PA PIP = ELR. Therefore once airflow becomes effort
independent P depends on ELR.

Flow-Volume Curves:
In obstructive ventilatory defect, the level of obstruction (intrathoracic or extrathoracic) / fixed or variable /
reversibility to bronchodilators can be assessed by FV curves. In restrictive defect, the stage of disease
(early or late) may be determined.

Mixed Airway Disease: Combination of both peripheral obstructive and restrictive abnormalities. Both curvilinear and
miniature shapes are seen. e.g. pneumoconiosis.

Restrictive Disease: Any disease which decreases lung expansion (chest wall diseases / space occupying
lesion in the pleural cavity / lung diseases) causes restrictive type of abnormality. In early interstitial lung
disease even before lung volumes are decreased, the FV curves usually show super-maximal expiratory
airflow associated with a steep descending limb of the curve (due to increase in lung elastic recoil) and the
curve becomes tall and narrow. In severe reduction of lung volumes, the FV curve maintains a relatively
normal shape but appears miniatured in all directions.
Peripheral Obstructive: most characteristic feature is the curvilinear shape (upward concavity) of
descending limb of curve. Recorded in diseases such as asthma, chronic bronchitis and emphysema. CD =
period of high flow. = Tidal volume loop moving towards vital capacity.

COPD: Primarily Emphysema

VC

LUNG VOLUMES
TLC RV
FRC

DYNAMIC LUNG VOLUMES

FVC

FEV1

FEV1/FVC
<0.8

FEV3/FVC

PEF

FEF

2575%

Patients problem is primarily expiratory.

No improvement in dynamic lung volumes after a bronchodilator this is not asthma.
Only sometimes produces sputum, does not appear to be cyanotic, and has a low DLCO:
more likely to be COPD: Primarily Emphysema (rather than CB). Usually patients often have a
combination of both.

RDs:
Lung volumes and capacities are all approximately two thirds of the predicted values. FEV1/FVC is greater
than predicted. Low DLCO.

During Inspiration
Intrapleural Pressure
Recoil Force
Alveolar Pressure

-5 -8

+5 +8

0 -1 0

During Expiration
-8 -5

+8 +5

0 +1 0

Changes in pressures during a normal respiratory cycle (in cmH2 O)

Exaggerated radial traction with wider tube diameter occurs in parenchymal restrictive diseases.

(L)

(L)

VT (ml)

RR

Deep Normal Breathing

600

10

4.5

Rapid Shallow Breathing

300

20

PaCO2

PaO2

pH

The person with rapid shallow breathing has a larger component of dead space ventilation. Even though total ventilation may be the same, alveolar ventilation is
depressed (this person is hypoventilating). When alveolar ventilation is low you tend to retain CO2 retaining CO2 by itself would lower the PO2. By definition
Physiologic dead space is the volume of gas that does not eliminate CO2.

AT FRC THE LUNG & CHEST WALL FORCES ARE AT EQUILIBRIUM (DEPICTED BY THE ARROWS).

STAGES OF VALSALVA

MAP
HR

Stage 1

Stage 2

Stage 3

Stage 4

VALSALVA: Duration of valsalva lasts from contraction of expiratory muscles until their relaxation (as shown by the arrow). First step is a deep inspiration
(at the end of deep inspiration the intra-thoracic pressure will be very ve & since the alveolar volume is increased the recoil force is high). The second step
is the valsalva maneuver itself (closing the glottis & contracting the expiratory muscles vigorously thus creating a very +ve intra-thoracic pressure). Recoil
force will be the same (because a closed glottis prevents any change in lung volume). Now both the +ve intrathoracic pressure and the increased lung recoil
act inwardly causing a rise in alveolar pressure (alveolar pressure = intrapleural pressure + recoil force).
Phase 1 (Onset): +ve intra-thoracic pressures compress the pulmonary vasculature transient increase in venous return to the left side of the heart ed
MAP reflex e in HR. This phase is just an exaggeration of normal expiration.

Phase 2 (Straining Phase): Severe compression of pulmonary vasculature decreasing VR to the left heart ed MAP relex e in HR. ing VR causes a
backing up of blood in the veins leading to a rise in CVP. VR ( CVP) CO MAP HR. Important for Dx. Less blood in the heart.
Phase 3 (Release): Further e in LV volume. Exaggeration of Phase 2.
Phase 4 (Overshoot): Opp. to 2 & 3.

NON-RESPIRATORY FUNCTIONS
Air-Conditioning: heated to body temperature and humidified
Filtration of the inspired air:

Particles > 10 m removed by vibrissae.

Impaction: Particles 5 10 m inspired air stream changes direction abruptly at the nasopharynx so that many of these particles impact on the
posterior wall of the pharynx (tonsils and adenoids are located near this impaction site, providing immunologic defense) & at carina or within large
bronchi. Fails to turn corners strikes a wet surface & is trapped there.

Sedimentation: Particles between 0.5 5 m sediment in the smaller airways (terminal & respiratory bronchioles) because of their weight. In
simple pneumoconiosis dust accumulates here ( micronodular mottling on CXR) if toxic fibrous reaction (Eg. silica dust). Many bacteria fall
within this size range. Target size for particles of inhaled medications is less than 5 m so that the medication can reach the more distal lung.

Particles between 0.1 - 0.5 m stay suspended as aerosols and are exhaled. They are neither too heavy to sediment nor too light to diffuse.
Diffusion: Particles < 0.1m are deposited in the alveolar ducts and alveoli as a result of brownian motion due to their bombardment by gas
molecules.

Bronchoconstriction to prevent deeper penetration of the irritant into the airways.

Removal of particulate matter entrapped in mucus:

[1] Airway Reflexes:

Sneeze results from stimulation of receptors in the nose or nasopharynx. In a sneeze the expiration is via the nose.

Cough results from stimulation of irritant receptors in the trachea. In a cough the expiration is via the mouth.

In either case, a deep inspiration to near the TLC is followed by a forced expiration against a closed glottis (intrapleural pressure may rise to more
than 100 mmHg) glottis opens suddenly pressure in the airways falls rapidly explosive expiration, with high linear airflow velocities
carry the irritant along with mucus out of the respiratory tract.

[2] Mucociliary Escalator: upper airways down to the terminal bronchioles, is lined by mucus-covered ciliated epithelium. Mucus is produced by mucus
glands & goblet cells. Directly adjacent to the cells is the sol layer, within which the cilia are located. Superficial to the sol layer is the more viscous gel layer,
which is produced by both submucosal mucous glands and goblet cells (viscous gel layer floats on top of the aqueous sol layer and is propelled upward as
the cilia beat freely within the less viscous sol layer). Important mechanism for the removal of inhaled particles that come to rest in the airways. Increased
removal during a cough. Patients who cannot clear their tracheobronchial secretions (an intubated patient or a patient who cannot cough adequately)
continue to produce secretions. If the secretions are not removed by suction airway obstruction develops. Mucus blanket moves at a rate of 1 mm/min in the
small peripheral airways & 2 cm/min in the trachea eventually reach the pharynx swallowed. Chronic Bronchitis & Bronchiectasis number of goblet
cells increase and the mucous glands hypertrophy increased mucous gland secretion & increased viscosity of mucus ciliary transport system is
overloaded. Thick tenacious mucus (like in asthma) cannot be propelled easily by the cilia (many of the airways are occluded by mucus plugs).
Removal of particulate matter from alveolar ducts & alveoli:

Alveolar Macrophages: Macrophages are unable to digest certain particles like silica (toxic to them) death of the macrophages silica
redeposited on the alveolar surface. Main exit routes: (1) Pores of Kohn adjacent healthy alveoli mucociliary escalator removal through
the airways. (2) interstitium lymphatics.

Penetration into the interstitial space or enter the blood, where they are phagocytized by interstitial macrophages or blood phagocytes.

Entrance into the lymphatics.

Nonspecific enzymatic destruction (macrophages contain lysozyme)

Pulmonary Circulation: Site of blood filtration and storage.

Because of its high compliance and the -ve PIP can store a blood volume of 500ml (typical adult male).

This large blood volume allows the pulmonary circulation to act as a reservoir for the left ventricle. If left ventricular output is transiently greater
than systemic VR, LV output can be maintained for a few strokes by drawing on blood stored in the pulmonary circulation.

Can filter stuff: small fibrin or blood clots / fat cells / bone marrow / detached cancer cells / gas bubbles, / agglutinated erythrocytes (especially in
sickle cell disease) / debris from stored blood or intravenous solutions. If these particles were to enter the arterial side of the systemic circulation,
they might occlude vascular beds with no other source of blood flow (not great for the brain or heart).

The lung can perform this because there are many more pulmonary capillaries present in the lung than are necessary for gas exchange at rest (

The mechanisms for removal of material trapped in the pulmonary capillary bed include lytic enzymes in the vascular endothelium / ingestion by

Cardiopulmonary bypass: pulmonary capillary filtration does not occur, and blood administered to these patients must be filtered for them.

unopened capillaries will be recruited).

macrophages / penetration to the lymphatic system. The diffusing capacity usually remains decreased for 4 to 5 days and then returns to normal.
Metabolism:

Prostaglandins E1 / E2 / F2 / Leukotrienes = completely removed in a single pass through the lungs

Prostaglandins I2 (Prostacyclin) = not affected

Serotonin = 85% to 95% removed (and stored in the lung). Not removed by enzymatic degradation. Some of the serotonin may be transferred to

Angiotensin I: Approximately 70% converted to angiotensin II by ACE (found on the surface of endothelial cells).

platelets in the lung or stored in some other way and released during anaphylaxis.

Bradykinin: 80% inactivated by ACE.

Epinephrine = not affected

Norepinephrine = 30% removed

Done by pulmonary vascular endothelium. Substances released into specific vascular beds for local effects are inactivated. Other substances
needed for more general effects in the systemic circulation are not affected. If a drug is metabolized here: it does matter whether you are
administering it via an arterial or venous catheter.

Pulmonary Surfactant: synthesized in type II alveolar epithelial cells and released at the alveolar surface.
Response to Injury: Type II cells can regenerate into both Tpe I & II cells repopulating them after an injury.

ALVEOLAR VENTILATION

RV: Depends on:

Expiratory muscle strength
Inward elastic recoil of the lung & Outward elastic recoil of the chest wall
Dynamic compression of the airways during a forced expiratory effort
Prevents the lungs from collapsing at very low lung volumes. Collapsed alveoli are difficult to reinflate.
Emphysema: ed alveolar elastic recoil / airway collapse and gastrapping
IRV & TLC: Depend on:
Inspiratory muscle strength
Inward elastic recoil of the lung & chest wall
FRC: At the end of a normal tidal expiration. ed in
3rd trimester pregnancy & obesity (outward recoil of chest wall ed)
Pulmonary fibrosis
VC: Volume of air expelled from the lungs during a maximal forced expiration starting after a maximal forced inspiration.
Depends on all above factors.

Standing Supine: ed outward elastic recoil of the chest wall (diaphragm moves up). FRC ( ERV / IRV & IC ). The
RV, VC, and TLC = no change (may e slightly because of ed VR ed intrathoracic blood volume). VT = no change. Opp
changes happen with standing.
RDs: ed elastic recoil of the lungs & ed compliance. All volumes compressed (ed). e in VT RR.
ODs:
ed resistance to airflow. Mucus plugs high PIP generated to overcome the ed airway resistance dynamic airway
compression (made worse by destruction of alveolar septa ed radial traction).
ed elastic recoil of the alveoli & ed compliance.
RV / FRC / TLC / VT ed. e in VT RR.
VC / ERV ed

FEV1 / FVC / FEF2575% and others = Can be measured by spirometry.

RV / FRC / TLC = Cannot be measured by spirometry. Use:
Nitrogen-washout technique = Breathes 100% O2 until all N2 has been washed out. N2 constitutes 80% of the total lung
volume.
Helium-dilution technique = If a known amount of a solute is dissolved in an unknown volume of solvent, and the
concentration of the solute can be determined, then the volume of solvent can be calculated. Helium = is not taken up by
blood (insoluble in blood).
Body plethysmography = Above 2 will not include the volume of trapped gas (within slow alveoli). This one does.
Makes use of Boyles law (for a closed container at a constant temperature, the pressure times the volume is constant).
Anatomic dead space = Measured by Fowlers method. Approx = 1 mL / pound of ideal body weight.
ed = bronchodilation / airway traction. ed = bronchoconstriction / airway compression
Alveolar (Functional) dead space = Volume of gas that enters unperfused alveoli per breath. A healthy person has little or no
alveolar dead space. ed in PE / Hemorrhage ( low RV output) / PEEP (ed alveolar pressure).
Physiologic dead space = anatomic dead space + alveolar dead space. Calculated using the Bohr Eqn. (Concept: Any
measurable volume of CO2 found in the mixed expired gas must come from alveoli that are both ventilated and perfused because
there is negligible amount of CO2 in inspired air). CO2 meter is used to estimate the PACO2 by analyzing the gas expelled at the end
of a normal tidal expiration (end-tidal CO2). Equilibrium occurs between the PCO2 of perfused alveoli and their end-capillary PCO2.
If PaCO2 > PACO2 (end-tidal CO2), then physiologic dead space is > anatomic dead space which means ed alveolar dead space.
Note: Instead of end-tidal CO2 you may also use PECO2 this result will also include anatomic dead space. The dot over the letter
V indicates per minute. The volume of air entering and leaving the nose or mouth per minute (minute ventilation) is not equal to
the volume of air entering and leaving the alveoli per minute (alveolar ventilation), because the last part of each inspiration
remains in the conducting airways and does not reach the alveoli.

Thus, if anatomic dead space is 150 mL & VT is 500 mL per breath, then only 350 mL of gas enters and leaves the alveoli per
breath. For 1 minute multiply by the RR:
Alveolar Ventilation = (VT VD) RR = (500 150) 12 = 4200 ml/min
Minute Ventilation = VT RR = 6000 ml/min
Slow deep breathing is more effective since a greater fraction of the fresh air in each breath actually enters the alveoli.

Test Gas = Helium (neither taken up nor liberated). At the end of expiration the conc. of test gas in the balloon is higher than that
in the alveolar air & anatomical dead space because it contains a mixture of pure test gas (from the anatomical dead space) &
diluted test gas (from the alveoli).

Daltons law = In a gas mixture, the pressure exerted by each individual gas is independent of the pressures of other gases in the
mixture.

Partial pressure (of a particular gas) = Fractional conc. (of that gas) The total press. (of all gases in the mixture) = F PB
Example: PO2 (dry atmospheric air) = 21% 760 mmHg (standard barometric pressure) = 160 mmHg

PIO2 = 0.21 (760 47) = 150 mmHg

As air is inspired through the upper airways, it is heated and humidified. Gas is diluted by the added water vapor.
PIO2 = PO2 of Inspired air (saturated with water vapor at standard barometric pressure)
FIO2 = fractional conc. of inspired O2
PB = barometric pressure = 760 mmHg = 1 atm
PH2O = water vapor pressure = 47 mmHg at 37C
Atmospheric air contains N2 (79%) / O2 (21%) / CO2 (very negligible, considered 0%).
Sum of all partial pressures will be equal to the total pressure & sum of all the fractional concentrations will be equal to 100%.

Atmospheric

Inspired

Alveolar

Mixed Expired

PO2

160

PIO2

150

PAO2

100

PEO2

120

PCO2

PICO2

PACO2

40

PECO2

27

PN2

600

PIN2

563

PAN2

573

PEN2

566

PH2O

PIH2O

47

PAH2O

47

PEH2O

47

Total

760

Total

760

Total

760

Total

760

VA: Each inspiration brings into the 3 L of gas already in the lungs (FRC), 350 mL of fresh air containing 21% O2, and
each expiration removes about 350 mL of air containing 6% CO2.
240 mL of CO2/min diffuses from the pulmonary capillary blood into the alveoli (PACO2 es by 2 to 4 mm Hg with each
inspiration and es slowly until the next inspiration).
300 mL of O2/min diffuses from the alveoli into the pulmonary capillary blood (P AO2 es by 2 to 4 mm Hg with each tidal
inspiration and es slowly until the next inspiration).
Because of these processes, the PAO2 and PACO2 are determined by the VA / pulmonary capillary perfusion / O2
consumption / CO2 production.
VA is normally adjusted by the respiratory control center to keep Pa CO2 & PACO2 at about 40 mm Hg.
Mixed Expired air is a mixture of about 350 mL of alveolar air and 150 mL of air from the dead space. Therefore, the
PEO2 is higher than alveolar PAO2 and lower than PIO2. Similarly, the PECO2 is much higher than the inspired PICO2 but
lower than the alveolar PACO2.

Alveolar Ventilation & CO2

ALVEOLAR VENTILATION EQUATION:

VCO2 = Rate of CO2 production from aerobic metabolism

VA = alveolar ventilation (ml/min)
Concentration of CO2 in the alveolar gas is dependent on the alveolar ventilation (excretes CO2 in expired air) and on the
rate of CO2 production by the body (and its delivery to the lung in the mixed venous blood).
In healthy people, alveolar PCO2 is in equilibrium with arterial PCO2. Thus, if VA is doubled (and CO2 production is
unchanged), then the alveolar and arterial PCO2 are reduced by one-half. If VA is halfed, then alveolar and arterial PCO2 will
double.
If CO2 production is doubled entire curve shifts to the right (To maintain PACO2 VA has to be doubled).

Alveolar Ventilation & O2

The highest PAO2 one could possibly achieve (breathing air at sea level) is the inspired PO2 of about 150 mm Hg. As VA es, the
alveolar PCO2 es, bringing the alveolar PO2 closer to the inspired PO2.
ALVEOLAR GAS EQUATION:

R = exchange ratio (or) respiratory quotient (CO2 production / O2 consumption). Normal = 0.8 (normally less CO2 is produced
than O2 consumed = because under resting conditions fat metabolism generates less CO2. During exercise R = 1 because
carbohydrate catabolism es, generating more CO 2 ).
O2 consumption = 3.4 ml/kg/min = approx 240ml/min (in a 70 kg person).
CO2 production = 4.3 ml/kg/min = approx 300 ml/min (in a 70 kg person).
R = 240/300 = 0.8
Examples:
[1] Normal VA: PAO2 = 150 40/0.8 = 100 mmHg
[2] VA Doubled: PAO2 = 150 20/0.8 = 125 mmHg
[3] VA Halved: PAO2 = 150 80/0.8 = 50 mmHg

Regional Differences in alveolar ventilation

In a subject seated in the upright posture and breathing normally from the FRC, the lower regions of the lung are relatively better
ventilated than the upper regions of the lung. Regional differences are because of gravity, with dependent regions better
ventilated than nondependent regions.
Because of the wt. of the lung, PIP is less ve (ed) at the base (gravity-dependent region) than at the apex.
Lower alveolus: less ve PIP smaller PTP smaller volume (than the upper alveolus). At FRC the lower alveolus is on a
more steep portion of the alveolar pressure-volume curve (i.e., it is more compliant). Base has both a larger change in volume & a
smaller resting volume than the apex.
Upper alveolus: opp. to above. Larger volume. Less steep portion of the alveolar pressure-volume curve (i.e., it is less
compliant).
Important: When you use the term hyperventilation (or) hypoventilation you are specifically talking
about alveolar ventilation & not total ventilation.

Above lung is at FRC with PA = 0. Y axis = volume of the alveolus expressed as a % of its maximum. This curve is drawn with
the pressure-volume characteristics of a single alveolus in mind. Any change in the transpulmonary pressure during a normal
respiratory cycle will cause a greater change in volume in the lower alveolus, than it will in the upper alveolus (as shown by the
arrow length in the figure). Because the lower alveoli have a greater change in volume per inspiration and per expiration, they are
better ventilated than the upper alveoli (during eupneic breathing from FRC). At FRC, most of the alveolar air is in upper regions
of the lung because those alveoli are larger. Most of the ERV is in the upper portion & most of the IRV and IC are in lower
portions of the lung.

Slow inspiration from RV after a maximal expiration. Initial part of the breath enters the nondependent upper alveoli &
dependent alveoli begin to fill later in the breath (normal distribution is inverted).
During Expiration: +ve PIP are generated by the expiratory muscles during a forced expiration to the RV (more +ve in
lower regions of the lung). Alveoli in lower regions have less alveolar elastic recoil (because of smaller volumes). Both
these cause PTP to become ve & dynamic compression of small airways to occur.
During Inspiration: Takes some time for the reversal of the above 2 factors. No air enters these alveoli during the first
part of the inspiratory effort (horizontal arrow) until sufficient ve PIP is generated to open these closed airways.
At RV the alveoli in the upper regions of the lungs are now on a much steeper portion of the pressure-volume curve.
They are more compliant at this lower lung volume.

SINGLE BREATH OF OXYGEN TEST (SBOT):

Pt takes a single VC inspiration (from RV to TLC) of 100% O2 followed by slow exhalation to RV

At RV (before inspiration) apex has more N2 than the base, simply because the apex has big alveoli & N2 is 80% of that
& also because during a VC breath of O2, this region expands less and therefore the N2 there is less diluted with O2.
Most of the 100% O2 will enter the more dependent alveoli
Phase 1: 100% O2 from the anatomical dead space. 0% N2
Phase 2: mixture of dead-space gas and alveolar gas
Phase 3: alveolar gas from the upper and lower lung regions (alveolar plateau). almost flat. In pts with uneven
ventilation phase 3 steadily rises (slope is a measure of ventilation inequality). This is because those alveoli that are
supplied by high-resistance airways (slow alveoli) fill more slowly (& therefore less completely) than those supplied
by the normal airways during the 100% O2 inspiration. Thus, they have a relatively higher N2 concentration. During
expiration they empty more slowly, and when they do, the expired N2 conc. rises. Represents uneven dilution of the
alveolar N2 by inspired O2.

Phase 4: Nearing RV the local PIP at the base es (becomes +ve) + smaller alveoli in the lower parts of the lung have
less elastic recoil airway closure first occurs at the base (N2 conc. low) more & more gas comes from the upper
regions (N2 conc. high) expired N2 conc. rises abruptly [preferential emptying of the apex (which has a relatively high
N2 concentration) of the lung after the lower-zone airways have closed].
Takeoff point of phase 4 (closing capacity) = beginning of airway closure in dependent portions of the lung.
Note: airway closure will proceed up the lung (but) down the individual airway.

THE AGING LUNG : Main change is a loss of pulmonary elastic recoil causing airway closure in dependent areas of the lung
at lower lung volumes.

No problem with routine activities. Reserves available to meet stresses compromised.

Loss of alveoli ed alveolocapillary surface area & ed pulm. capillary blood volume ed pulm.
diffusing capacity e in PaO2. (alveolar-arterial O2 difference es with age)
Enlargement of terminal air spaces
ed elastic lung (alveolar) recoil force ed static lung compliance
ed (outward) elastic recoil of the chest wall ed chest wall compliance. (Calcification of costal cartilages
/ decreased spaces between the spinal vertebrae / greater degree of spinal curvature). Chest wall factors e
the WOB.
ed lung recoil force + ed chest wall recoil force ed FRC
ed elastic lung (alveolar) recoil force ed traction on small airways (to oppose dynamic compression
during forced expirations) small airway closure at higher lung volumes (ed closing capacity & ed
closing volume). Small airway closure may occur in dependent airways even at volumes above FRC (see pic).
Relatively more ventilation of upper airways (compared to younger individuals). ed ELR also leads to ed
driving pressures for airflow.
ed resp. muscle strength
Dynamic compression + ed resp. muscle strength ed RV and ed maximal expiratory flow rates (FEF2575% & FEV1).
e in RV (due to airway closure) is > than the e in FRC ERV will e

IRV, IC & VC are all ed

CC & CV ed
TLC & VT= stays constant with age
ed ventilatory response to hypercapnia and hypoxemia
ed frequency of bacterial infection (pneumonias)

To maintain the same flow the velocity has got to be doubled.

ROOM AIR (21% O2)

100% O2

Alveolus

Arterial

Venous

Alveolus

Arterial

Venous

40

40

45

40

40

45

100

100

40

673

673

55

47

47

47

47

47

47

N2

573

573

573

TOTAL

760

760

705

760

760

147

CO2
O2
H2O

PULMONARY CIRCULATION
Respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli, receive O2 directly by diffusion
from the alveolar air and nutrients from the mixed venous blood in the pulmonary circulation. The
remaining structures supplied by the bronchial arteries (part of the systemic circuit high
pressures). Most of the brochial venous blood enters the pulmonary vein (unusual. part of the
normal anatomic right-to-left shunt). Bronchopulmonary anastomoses: between bronchial
and pulmonary capillaries. Normal conditions no role. If pulmonary blood flow to an area of the
lung is blocked (by a pulmonary embolus), bronchial blood flow to that area increases.
Pulmonary vascular resistance = Pulmonary circuit has thin walls (less vascular smooth muscle)
at all levels / has greater internal diameters / is more distensible / & has nothing akin to arterioles
(when compared to the systemic circuit) all lead to ed resistance to blood flow and ed
pressures. PVR is 1/10th that of SVR (TPR). Assuming MPAP & LAP of 15 and 6 mm Hg, respectively,
along with a CO of 6 L/min, the pulmonary resistance is (15 6)/6 = 1.5 mmHg/L/min. Resistance
is evenly distributed among the three components of the pulm. circuit: pulmonary arteries,
pulmonary capillaries, and pulmonary veins. Work load of RV < LV. More distensible and
compressible therefore subject to outside forces (or) passive factors (i.e influenced by factors
other than the smooth muscle tone. Gravity, body position, lung volume, alveolar and intrapleural
pressures, intravascular pressures, and right ventricular output will all have major effects on PVR
without any alteration in pulmonary vascular smooth muscle tone.). For distensible-compressible
vessels, the transmural pressure gradient is an important determinant of the vessel diameter:
ing PTM ed resistance and viceversa. ed interstitial pressures ( compression) & ed blood
viscosity will e R.
Lung Volume & PVR:
[1] Alveolar vessel (AV): vessels found between alveoli (pulmonary capillaries)
[2] Extra-alveolar vessel (EAV): Includes [a] larger arteries & veins, [b] corner vessel (or)
extra-alveolar capillary (found at junctions of alveolar septa)
AV & EAV are in series. To calculate total resistance just add.

During Inspiration:
e in alveolar volume AV is elongated ( length) and compressed (r) R es.
ed alveolar volume ed radial traction on EAV wall by alveolar septa R es.
More ve PIP PTM of EAV es R es.
Thus, at high lung volumes (attained by normal negative-pressure breathing), the resistance
to blood flow offered by AV es and EAV es.
During Expiration : Forced expiration to low lung volumes PIP becomes very +ve.
More +ve PIP PTM of EAV es (becomes ve) R es (collapse)
ed alveolar volume ed radial traction on EAV wall by alveolar septa R es.
AV exhibits ed R
Thus, at low lung volumes (attained by normal negative-pressure breathing), the resistance
to blood flow offered by EAV es and AV es.
Total PVR (U-shaped curve) is lowest near FRC and es with both high and low lung volumes.

Mechanical Ventilation (+ve pressure ventilation): Both PA and PIP are +ve during inspiration
Both AVs and EAVs are compressed R will e (especially with PEEP).
With PEEP:
Airway pressure (and thus alveolar pressure) is kept positive at end expiration to help
prevent spontaneous atelectasis (used for this). Thus PA and PIP are positive during both
inspiration and expiration. PVR is elevated in both alveolar and extraalveolar vessels
throughout the respiratory cycle. Workload placed on the RV increases and its output will e.
Normally ve intrathoracic pressure during inspiration promotes VR from the periphery. +ve
inspiratory (and expiratory in PEEP) pressure from a ventilator es venous return to the
heart.
ed VR and ed PVR will e CO precipitously (treat with fluid loading).
ed PA compression & de-recruitment of AVs R
+ve PIP es VR es pulm. blood flow derecruitment R. The +ve PIP will also
compress EAVs.
Recruitment & Distention
There is a e in PVR in response to ed blood flow (CO) / ed perfusion pressure (MPAP) / ed
pulmonary blood volume / ed LAP (i.e ing venous pressures). Explained by the below 2
mechanisms.

Recruitment of pulmonary capillaries occurs initially with small increases in pulmonary vascular
pressures. Distention occurs later at higher pressures.
ing blood flow es the mean pulmonary artery pressure which opposes hydrostatic forces and
exceeds the critical opening pressure in previously unopened vessels opens new parallel pathways
(Recruitment) PVR es. es the surface area for gas exchange & es alveolar dead space. ing RV
output / ing pulmonary artery pressure (or) ing alveolar pressures result in a derecruitment.
e in perfusion pressure ed PTM Distension PVR es.
Moderate Exercise: CO MPAP Recruitment / Distension e in PVR
Blood loss: VR CO MPAP Derecruitment / ed Distension e in PVR

Humoral Pulmonary Vasoconstrictors: Histamine (found in the lung in mast cells acts as a venoconstrictor
in the lung) / certain prostaglandins / thromboxane / endothelin (synthesized by the vascular endothelium) /
alveolar hypoxia and hypercapnia / low pH of mixed venous blood / angiotensin.
Humoral Pulmonary Vasodilators: Ach / NO / certain prostaglandins / prostacyclin / isoproterenol / bradykinin.
Neural (Sym VC & PS VD) and humoral factors produce active changes in PVR, as opposed to passive
changes.
Total pulmonary blood flow(=CO) measurement: Fick principle / indicator dilution technique / thermal dilution
technique (quadruple-lumen swan-ganz catheter is used in TDT).
Regional pulmonary blood flow: pulmonary angiography / lung scans after injection of macroaggregates of
albumin labeled with radioactive substance / lung scans after the infusion of dissolved radiolabeled gases
(Xenon is not a very soluble gas, and so it comes out of solution in the lung and enters the alveoli).

Regional Distribution of Blood Flow

The units of blood flow are such that if flow were uniform, all values would be 100. For the
measurement of blood flow, the xenon is dissolved in saline and injected into a peripheral vein.
When it reaches the pulmonary capillaries, it evolves into alveolar gas because of its low solubility,
and the distribution of radioactivity can be measured by counters over the chest during
breathholding. Considerable inequality of blood flow exists within the human lung (explained by
hydrostatic pressure differences within the blood vessel due to gravity). If we consider the
pulmonary arterial system as a continuous column of blood, the difference in pressure between the
top and bottom of a lung 25 cm high will be about 25 cm water, or 19 mm Hg. This large pressure
difference (for such a low-pressure system) will result in uneven distribution of blood flow in the
lungs. Pressure in pulmonary vessels at the apex is 19 mmHg lower than in pulmonary vessels at
the bases. Vascular pressures (pulmonary arterial and venous) depend in part on the vertical
location of the vessels in the lung because of the hydrostatic effect. There is greater blood flow per
unit volume to lower (correctly called gravity dependent) regions of the lung than to upper regions
of the lung. Exercise tends to offset the gravitational effects in an upright person. As cardiac
output increases with exercise, the ed pulmonary arterial pressure leads to capillary recruitment
and distention in the lungs apex, resulting in ed blood flow and minimizing regional differences in
blood flow in the lungs. The pressure at the bottom of a column of a liquid is proportional to
the height of the column times the density of the liquid times gravity. Gravity dependent
area of the lung ed intravascular pressures e in resistance (owing to recruitment and
distension) ed blood flow & at a faster rate (i.e ed mean capillary transit time) in the lower
regions of the lung.
The Zones of the Lungs: Interaction of gravity & extravascular pressure: Experiment done
on excised / perfused / upright animal lung model at low pump outputs so that the pulmonary
artery pressure was low. As you go down Pa es / PTM es / capillaries distended / PVR es.
Zone 1: PA > Pa > Pv = No blood flow (alveolar pressure exceeds arterial and venous pressures).
Capillaries are squashed flat, and no flow is possible. Ventilated but unperfused lung = alveolar
dead space. Under normal conditions: there is no zone 1, because the pulmonary arterial pressure
is just sufficient to raise blood to the top of the lung, but may be present if the arterial pressure is
reduced (severe hemorrhage / during general anesthesia / astronauts during a spacecraft launch)

or if alveolar pressure is raised (positive pressure ventilation with PEEP: PA is always high).
Following will e the tendency toward zone 1 conditions: High altitude & moderate exercise In
both states MPAP will e because of HPV & CO respectively. Standing Supine: es the
hydrostatic pressure gradient that must be overcome to perfuse nondependent portions of the lung
(&) also es VR & CO.

Zone 2: Pa > PA > Pv = Pa increases because of the hydrostatic effect and now exceeds alveolar
pressure. However, venous pressure is still very low and is less than alveolar pressure. The effective
driving pressure for blood flow = Pa PA (not the usual a-v pressure difference). The functional
importance of this is that venous pressure in zone 2 has no effect on flow, unless it exceeds alveolar
pressure. The increase in blood flow per distance down the lung is greater than it is in zone 3,
because the upstream driving pressure (Pa) increases but the effective downstream pressure (PA) is
same throughout the lung at any instant. ing recruitment of capillaries occurs down this zone.
Blood flow is greater at the bottom than at the top of this zone.
Zone 3: Pa > Pv > PA = Venous pressure now exceeds alveolar pressure, and flow is determined in
the usual way by the a-v press. diff. (effective driving pressure for blood flow is simply Pa Pv).
The increase in blood flow down this region of the lung is caused by distension of the capillaries.
The driving pressure stays constant as one moves further down the lung in zone 3 (because the
hydrostatic pressure effects are the same for both the arteries and the veins).
Hypoxic Pulmonary Vasoconstriction (HPV): Alveolar hypoxia or atelectasis causes an active
precapillary vasoconstriction in the pulmonary circulation (vessels close to the alveoli). Hypoxia
closes K+ channels in pulmonary vascular smooth muscle cells ed efflux depolarization
allows Ca2+ entry contract (hypoxia acts directly on pulmonary vascular smooth muscle to
produce HPV). The response occurs only in the area of the alveolar hypoxia. Begins to occur at PAO2
of 100 mmHg. Below 70 mmHg marked vasoconstriction. Alveolar hypercapnia also causes
pulmonary vasoconstriction by an unknown mechanism. Localized HPV: Diverts mixed venous
blood flow away from poorly ventilated areas to better-ventilated areas of the lung.

L: Normal alveolar-capillary unit. R: Perfusion of a hypoventilated alveolus results in blood with a ed PO2 and
an ed PCO2 mixing with blood draining well-ventilated areas of the lung. This mixing will lower the overall PaO2
and may even increase the PaCO2.

L: HPV increases the resistance to blood flow to the hypoventilated alveolus. R: Diverts blood flow away from
the hypoventilated alveolus to better-ventilated alveoli, thus helping to maintain V/Q matching.

Whole Lung HPV: (High altitude / Hypoventilation) es MPAP unperfused pulmonary

capillaries recruited es surface area available for gas diffusion better V/Q matching. ed
workload on the RV. The pulmonary artery pressure may overwhelm hypoxic pulmonary
vasoconstriction in some parts of the lung, increasing the capillary hydrostatic pressure in those
vessels leading to pulmonary edema.
Pulmonary Edema: Inevitably leads to impaired gas transfer. Edema fluid builds up (first in the
interstitium and later in alveoli) diffusion of gases (particularly O2) es. The capillary endothelium
is much more permeable to water and solutes than is the alveolar epithelium. Edema fluid therefore
accumulates in the interstitium before it accumulates in the alveoli. Keeping the alveoli free of fluid
is critical.

Plasma colloid osmotic pressure = 25 to 28 mm Hg. es with hypoproteinemia or

overadministration of Saline. The capillary hydrostatic pressure (approx. 10 mmHg) is about
halfway between arterial and venous pressure but is much higher at the bottom of the lung than at
the top. Often increases secondary to problems in the left side of the circulation such as LVF & MS.
As left atrial pressure and pulmonary venous pressure rise the pulmonary capillary hydrostatic
pressure also increases. Other causes: too much IV fluids. Interstitial hydrostatic pressure =
range of -5 to -7 mm Hg. Conditions that would decrease the interstitial pressure would increase
the tendency for pulmonary edema to develop (Too rapid evacuation of pneumothorax or
hemothorax / decreased amounts of pulmonary surfactant). Net pressure of the Starling equation is
outward, causing a small lymph flow under normal conditions. Two possible paths for the fluid that
moves out of pulmonary capillaries. Fluid that enters the interstitium initially finds its way into the
perivascular and peribronchial spaces. Later fluid may cross the alveolar wall, filling alveolar spaces.
[1] Fluid leaks out into the interstitium of the alveolar wall tracks to the perivascular &
peribronchial interstitium (PA / PV / Bronchi / lymphatics enclosed in a sheath) fluid travels
via lymphatics to the bronchial & hilar nodes. Alveoli themselves are devoid of lymphatics. Pressure
in the perivascular space is low, thus forming a natural sump for the drainage of fluid. Earliest
form of pulmonary edema is characterized by engorgement of the peribronchial / perivascular
interstitium (cuffing) and is known as interstitial edema (ed lymph flow + some widening of the
interstitium of the alveolar wall)
[2] With time the lymphatics become overloaded and pressure in the interstitium es fluid
crosses the alveolar epithelium into the alveolar spaces alveoli fill with fluid one by one (alveolar
edema) arterial hypoxemia. ed lymph flow. Alveolar edema is much more serious than
interstitial edema because of the interference with pulmonary gas exchange.
Etiology:
ed permeability: Infections / circulating or inhaled toxins / O2 toxicity / factors that destroy the
integrity of the capillary endothelium / Acute respiratory distress syndrome
Others: head injury (neurogenic pulmonary edema) & heroin overdose in both cases reason
unknown.
High-altitude pulmonary edema: caused by high pulmonary artery pressures secondary to HPV
(HPV is uneven stress failure).
1) Terminal bronchioles are the smallest airways without alveoli.
2) Respiratory bronchioles belong to the transitional zone because they contain a few alveoli
in their walls.
3) Airways become narrower / shorter / numerous as they penetrate deeper into the lung.
4) The first 16 generations make up the conducting zone & the last 7, the respiratory zone.
5) Portion of lung distal to a terminal bronchiole forms an anatomical unit called the acinus.
6) There is an extremely rapid increase in total cross-sectional area of the airways in the
respiratory zone.
7) The anatomic dead space is the volume of the conducting airways.
8) The physiologic dead space is the volume of lung that does not eliminate CO 2. It is
measured by Bohr's method using arterial and expired CO 2.
9) Dynamic compression limits air flow in normal subjects during a forced expiration.
10) At very low lung volumes, the small airways may close completely, especially at the
bottom of the lung, where the lung is less well expanded.
th
th
11) During mouth breathing the resistance is greatest in the medium sized airways (5 to 7
generations).
12) < 20% of airway resistance can be attributed to airways smaller than in generation 8.
13) Because the small airways constitute a silent zone, it is probable that considerable small
airway disease can be present before the usual measurements of airway resistance can detect an
abnormality.
14) 30% of the total resistance to airflow is located in the upper airways, upto the Larynx.
15) Diseases of the central airways have a significant impact on total resistance in the lung
and are detected early, whereas diseases of the small airways show up late on testing (this region
is therefore called the silent zones of the lungs).

VENTILATION PERFUSION RELATIONSHIPS

Figure: The effect of changes in the ventilation-perfusion ratio on the alveolar PO2 and PCO2. A: Normal V/Q B:
V/Q = 0 C: V/Q is infinite. Below: The ventilation-perfusion ratio line on an O2-CO2 diagram. Unit with a
V/Q of zero has the PO2 and PCO2 of mixed venous blood; a unit with an infinite V/Q has the PO2 and PCO2 of
inspired air. Note that V is actually VA (alveolar ventilation) and not VE.
Concentration gradients (needed for passive diffusion of O2 & CO2) are maintained by ventilation of the alveoli
and perfusion of the pulmonary capillaries. Alveolar ventilation = 4 to 6 L/min and pulmonary blood flow (CO) is
also 4 to 6 L/min. V/Q for the whole lung = 0.8 to 1.2. Must be matched on the alveolar-capillary level. At
resting cardiac outputs the diffusion of both O2 and CO2 is normally limited by pulmonary perfusion. Thus, the
PAO2 and PACO2 are determined by V/Q. The partial pressure gradient for O2 diffusion from alveolus to pulmonary
capillary is 60 mm Hg; the partial pressure gradient for CO2 diffusion from pulmonary capillary to alveolus is 5
mm Hg. The position of the V/Q ratio line is altered if the partial pressures of the inspired gas or mixed venous
blood are altered. Note: Think of ventilation bringing in O2 and removing CO2 form the alveolus. Think of
perfusion bringing in CO2 & removing O2 from the alveolus. Alveolar PO2 and PCO2 thus depend on the
relationship between alveolar ventilation and perfusion.

V/Q ratios close to 1.0 result in PAO2 of 100 mmHg and PACO2 of 40 mm Hg
If V/Q es (>1) PAO2 es & PACO2 es. Extreme case: Gas composition of alveolus moves towards
inspired air. V/Q = Infinity (If you are sitting on 0 you dont know where you will end up). Will
correspond to zone 1. Alveolar dead space.
If V/Q es (<1) PAO2 es & PACO2 es. Extreme case: Gas composition of alveolus moves towards
mixed venous blood (line drawn over a letter refers to mixed). V/Q = 0. RL shunt.

Lung Model: Powdered dye poured into the unit (O2). Water is pumped continuously through the base of the
unit (blood flow) - that removes the O2. The concentration of dye in the alveolar compartment (PAO2) and,
therefore, in the effluent water (PaO2) will depend on the ratio of
[1] rate at which the dye is added, V (ventilation)
[2] rate at which water is pumped, Q (blood flow)

Uneven ventilation: Because of uneven resistance to airflow or uneven compliance. Uneven Resistance to
airflow: collapse of airways (emphysema); bronchoconstriction (asthma); decreased lumen diameter due to
inflammation (bronchitis); obstruction by mucus (asthma or chronic bronchitis); or compression by tumors or
edema. Uneven compliance: fibrosis, regional variations in surfactant production, pulmonary vascular
congestion or edema, emphysema, diffuse or regional atelectasis, pneumothorax, or compression by
tumors or cysts.
Uneven perfusion of the lung:embolization or thrombosis; pulmonary vessel compression (by high alveolar
pressures, tumors, edema, pneumothorax, or hydrothorax); destruction / occlusion of pulmonary vessels;
pulmonary vascular hypotension; collapse / overexpansion of alveoli.
Tests for Uneven (non-uniform) Ventilation:
[1] Single breath of O2 Test: rising expired nitrogen concentration in phase III (alveolar plateau of closing
volume test.)
[2] Nitrogen-Washout Test: Breathe normally from a bag of 100% oxygen, and the expired N2 concentration
is monitored over a number of breaths. With each successive inspiration of 100% oxygen and subsequent
expiration, the expired end-tidal nitrogen concentration falls (by the same fraction) as nitrogen is washed out of
the lung. Slower washout of alveolar nitrogen: seen with FRC / TV / Dead space / RR. Pt breathing normally
who take more than 7 minutes to reach an alveolar N2 concentration of less than 2.5% ed high resistance
pathways, or slow alveoli [short period of relatively rapid nitrogen washout (fast ventilated alveoli) followed
by a long period of extremely slow nitrogen washout (slow ventilated alveoli)]. Normal = straight line. This
method is also used for lung volume (FRC and therefore RV) measurement but there you completely washout
all N2 from the lung (1st graph = N2 is 80% of TLV which will give you an approximate estimate). But here you
are more interested in the rate of N2 washout.

[3] Trapped Gas: Differences between the FRC determined by the helium-dilution technique (or) nitrogen
washout technique and the FRC determined using a body plethysmograph indicates gas trapped in the
alveoli because of airway closure (Nitrogen trapped in alveoli supplied by closed airways cannot be washed out
and the helium cannot enter alveoli supplied by closed airways). If ed high resistance pathways takes
exceptionally long time for:
the patients expired end-tidal helium concentration to equilibrate with the helium concentration in the
spirometer (or)
all of the nitrogen to wash out of the patients lungs.
Therefore for lung volume measurements body plethysmography is much more accurate.
[4] Radioactive markers: Pictures of the whole lung taken with a scintillation counter, after pt. has taken a
breath of a radioactive gas mixture (like radioactive Xenon). Can Localize (unlike other 3).
Tests for Uneven (non-uniform) Perfusion:
[1] Pulmonary angiography: use radiopaque dye
[2] Lung scans after injection of macroaggregates of albumin (of a particular size range) labeled with
radioactive substance (radioactive iodine or technetium): get trapped in the lung. Aggregates fragment and are
spontaneously removed.
[3] Lung scans after the infusion of radiolabeled gases dissolved in saline (Xenon is not a very soluble gas, and
so it comes out of solution in the lung and enters the alveoli).
All 3 methods can locate the region of poor perfusion.

Testing for Mismatched Ventilation & Perfusion (V/Q)

Mismatching of ventilation and blood flow is responsible for most of the defective gas exchange in pulmonary
diseases. Testing for mismatched V/Q includes:
[1] Measuring Physiologic Shunt (The Shunt Equation)
[2] Measuring Alveolar Dead Space [(a-A)DCO2]
[3] Alveolar arterial O2 difference [(A-a)DO2]
[4] Lung scans after inhaled & infused markers
[5] Multiple Inert Gas Elimination Technique
Physiologic Shunt (The Shunt Eqn.): RL. Corresponds to the physiologic dead space. 1+2+3. 2+3 =
Intrapulmonary shunt (blood passes through the pulmonary capillaries). Whatever the etiology, the net
effect of the addition of poorly oxygenated blood is a e in PaO2.
[1] Anatomic shunts: 25% of the CO. Venous blood from the bronchial veins, pleural veins & the thebesian
veins (small amount of coronary venous blood drains directly into the cavity of the left ventricle) enter the left
side without passing through the pulmonary capillaries. Pathologic RL intracardiac shunts (TOF) &
pulmonary A-V fistulas also included here.
[2] Absolute Intrapulmonary Shunts (or) True Shunts: Mixed venous blood perfusing pulmonary
capillaries associated with totally unventilated or collapsed alveoli.
[3] Shunt-like States (V/Q) : Alveolar-capillary units with low V/Q (alveoli are underventilated and/or
overperfused). Act to lower the arterial oxygen content (CaO2) because blood draining these units have a lower
PO2.
The Shunt Equation: QS/QT (or) venous admixture (or) shunt fraction

QT = Total Flow = CO
QS = Shunt Flow (flow through shunted units) = amount of blood flow per minute entering the systemic
arterial blood without receiving any oxygen
QT QS = Normal Flow (flow through normal V/Q units)
CaO2 = arterial O2 content (ml O2/100ml of Blood)
CvO2 = end-capillary O2 content of shunted units = mixed venous O2 content
CcO2 = end-capillary O2 content of normal V/Q units (O2 content of the blood at the end of the pulmonary
capillaries with well-matched ventilation and perfusion)
Amount of O2 in systemic arteries = Amount of O2 from Normal units + Amount of O2 from
shunted units
Shunt Fraction [QT CaO2] = [(QT QS) CcO2] + [QS CvO2]
Dot means per min/ Line means mixed / Prime means end capillary.
On rearranging you will get the below formula.
CaO2 and CvO2 are calculated from arterial and mixed venous blood gas measurements, respectively.
CcO2 is estimated from the PAO2.

Ratio of shunt flow to the cardiac output (QS/QT / venous admixture / shunt fraction) is the portion of the CO
perfusing absolutely unventilated alveoli & is expressed as a percentage of the cardiac output. CcO2 cannot be
measured directly (calculated from the alveolar gas equation & the pts Hb conc). The arterial & mixed venous
(pulm. artery) O2 contents are easily determined. To differentiate between true intrapulmonary shunts
and the shuntlike states (V/Q) 100% oxygen for 20 to 30 minutes newly calculated value will
represent only the true shunt (with 100% O2 even alveoli with very low V/Qs will have high enough alveolar
PAO2 to completely saturate the Hb in the blood perfusing them these units will therefore no longer contribute
to the calculated QS/QT). True shunt = hypoxemia cannot be corrected with 100% O2. Some elevation of the
PaO2 occurs because of the O2 added to the capillary blood of ventilated lung. Most of the added O2 is in the
dissolved form, rather than attached to hemoglobin, because the blood that is perfusing ventilated alveoli is
nearly fully saturated. A shunt does not raise PaCO2 even though the shunted blood is rich in CO2
(chemoreceptors will sense any elevation of PaCO2 and respond by increasing ventilation).
Breathing 100% oxygen can be used to diagnose a shunt:
Picture. The addition of a small amount of shunted blood with its low O2 concentration (desaturated) greatly
reduces the PaO2. A shunt can be diagnosed by having the subject breathe 100% O2 for 15 minutes. PO2 in
systemic arterial blood in a patient with a true shunt does not increase above 150 mm Hg during the 15-minute
period. The shunted blood is not exposed to 100% O2, and the venous admixture reduces PaO2. If the PaO2 is
>150 mm Hg, the cause is a V-Q mismatch.

Alveolar-arterial O2 Difference [(A-a)DO2]:

Normal: 5 15 mmHg (because PAO2 is normally 100 and PaO2 is 85-95). The A-a O2 gradient is obtained from
blood gas measurements and the alveolar gas equation to determine PAO2. es with age (es by about 20 mmHg
between the ages of 20 and 70). The PaO2 is normally a few mm Hg less than the PAO2. This is caused by the
following in ing order of importance:
[1] Some degree of V-Q mismatch
[2] Normal anatomic shunt
[3] Diffusion limitation in some parts of the lung
V-Q mismatch & shunting (both ed venous admixture) are the 2 most important causes of a pathalogical
rise. es with age.

CAUSES:

ed RL shunt (desaturated blood combines with fully saturated blood and lowers PaO2): Intracardiac
lesions, pulmonary AVM, filling of the alveolar spaces with fluid / complete alveolar collapse.
V/Q mismatch: low V/Q areas provide relatively desaturated blood with a low O2 content. Blood
coming from regions with a high V/Q ratio cannot compensate for this problem, inasmuch as the Hb is
already fully saturated and cannot increase its O2 content further by increased ventilation.
True shunt (V/Q = 0) and V/Q mismatch (with areas of V/Q that are low but not 0) can be
distinguished by having the patient inhale 100% O2. In the former, ing PIO2 does not add more O2 to
the shunted blood, and O2 content does not increase significantly. In the latter PaO2 rises substantially.
In both cases (shunt & ed V/Q) - ed A-a is because of venous admixture.
Diffusion Block: PO2 in pulmonary capillary blood does not reach equilibrium with alveolar gas. Even
with thickened alveolar walls there is usually sufficient time for equilibration. Unless the transit time of
erythrocytes through the lung is significantly shortened (like in interstitial lung disease during exercise)
failure to equilibrate does not appear to be a problem.
When hypoventilation is the sole cause of hypoxemia, (A-a)DO2 is normal.
Low mixed venous PO2
Breathing higher than normal O2 concentrations
Shifts of the ODC

Picture: (L) Hypoventilation depresses the PO2 in the alveolar gas and, therefore, in the tissues.
(R) a slight e in PO2 contributing to the normal A-a O2 Difference.
PAO2/FIO2: PaO2/FIO2 is a common measure of oxygenation. A normal PaO2/FIO2 ratio is 300 to 500 mmHg,

with values < 200 mmHg indicating severe hypoxemia. example: a pt whose PaO2 is 60 mmHg while receiving
an FIO2 of 0.50 (ie 50 percent) has a PaO2/FIO2 ratio of 120 mmHg.

Alveolar Dead Space [(a-A)DCO2]:

Corresponds to infinite V/Q (ventilated but not perfused)

PaCO2 > PACO2 (end-tidal CO2) i.e ed [(a-A)DCO2] indicates the presence of alveolar dead space
(Normally both are equal).
[(a-A)DCO2] = arterial-alveolar CO2 difference
PACO2 is ed because CO2 is not excreted into the alveolus.

Because CO2 excretion depends on alveolar ventilation, PaCO2 will rise unless there is an overall
increase in the minute ventilation (which is usually the case).

Regional V/Q Differences in the Upright Lung:

Upper
Lung

Ventilation

Perfusion

V/Q Ratio

PIP more ve

Lower intravascular pressures

Higher (>1)

Greater PTM gradient

Less recruitment & distention

Alveoli larger & less compliant

Higher resistance

More ventilation than

flow

Less ventilation

Less blood flow

High PAO2 & Low PACO2

Greater intravascular pressures

Lower (<1)

More recruitment & distention

More flow than

ventilation

PIP less ve
Lower
Lung

Smaller PTM gradient

Alveoli smaller & more
compliant
More ventilation

Lower resistance
More blood flow

Low PAO2 & High PACO2

Because of higher V/Q in the upper lung more ventilation than flow if pulmonary perfusion
pressure is low (hemorrhage) or if alveolar pressure is high (positive-pressure ventilation with PEEP)
areas of zone 1 (with infinite V-Q ratios) in the upper parts of the lung. High V-Q ratio at the apex
results in a high PO2 and low PCO2 there. The opposite is seen at the base. PAO2 (horizontal axis)
decreases markedly down the lung, whereas the PACO2 (vertical axis) increases much less (PCO2
depends more on alveolar ventilation). High PO2 at the apex therefore TB seen here.

Top line = apex & bottom line = base

Volume of apex is less
PO2 changes by over 40 mm Hg, whereas the difference in PCO2 between apex and base is much
less
Difference in pH = PCO2 of the blood
O2 content of the blood draining the upper regions is higher.
CO2 content of the blood draining the upper regions is lower.
Inspite of all this the overall O2 uptake & CO2 loss is lower for the apex (because of a much
less blood flow and a smaller total volume) when compared to the base.
Respiratory exchange ratio (CO2 out / O2 in) is higher at the apex than at the base.
Exercise distribution of blood flow becomes more uniform apex assumes a larger share of
the O2 uptake

Picture: PAO2 at the apex is some 40 mm Hg higher than at the base of the lung. However, the major
share of the blood leaving the lung comes from the lower zones, where the PAO2 is low. This has the
result of depressing PaO2. By contrast, the expired alveolar gas comes more uniformly from apex and
base because the differences of ventilation are much less than those for blood flow. The relative sizes
of the airways and blood vessels indicate their relative ventilations and blood flows. Because most of
the blood comes from the poorly oxygenated base, e in PaO2 is inevitable. By the same reasoning,
PaCO2 will be elevated because it is higher at the base of the lung than at the apex. However, in
practice, patients with a known V/Q inequality often have a normal PaCO2. Whenever the
chemoreceptors sense a rising PaCO2, there is an increase in ventilatory drive returning PaCO2 to
normal (the linear shape of the CO2 dissociation curve allows more CO2 to diffuse from the
nonshunted blood into well-ventilated alveoli and be exhaled). On the other hand, increasing alveolar
ventilation cannot get any more O2 into the shunted blood and, because of the shape of the ODC,
very little more into the unshunted blood [After Hb is saturated with O2 (on the flat part of the ODC),
ing PaO2 does not significantly e the O2 content].
Example(Partial obstruction of Right main-stem bronchus): V/Q ratio of Right lung es (some
RL shunt / shunt fraction Qs/QT es) PAO2 & PACO2 HPV diverts some blood flow away from
hypoxic and hypercapnic alveoli to the better-ventilated left lung (but this response never functions
perfectly) PaO2 will e.
Apex
Base

Volume

V /Q

PO2

PCO2

O2 Content

CO2 Content

pH

O2 In

CO2 Out

Average V/Q for the whole lung is 0.8 (V/Q highest at apex & lowest at base). V/Q can be (dead space)/ High / Low / 0 (shunt). V & Q in l/min. O2
& CO2 Content in ml/dl. O2 In & CO2 Out in ml/min. Ultimately the base inspite of ed V/Q contributes more O2 and gets rid of more CO2 because of
the ed volume & ed blood flow.

Low V/Q = Regional alveolar hypoventilation. Caused by obstructed airway (mucus / object / bronchoconstriction) / ed lung compliance (fibrosis
/ edema). High V/Q = Regional hypoperfusion. Caused by PE / ed blood volume / +ve pressure ventilation (esp. PEEP) / ed CO (general
anesthesia does this).
V/Q mismatch is minimized by 2 pulmonary responses:
[1] Hypoxic Vasoconstriction: reduces flow to hypoxic alveoli
[2] Hypocapnic Bronchoconstriction: ed V/Q ed PACO2 local bronchoconstriction ed alveolar ventilation

DISTRIBUTION OF V-Q RATIOS:

Left: Distribution of V-Q ratios in a young normal subject. Note the narrow dispersion and absence of shunt. All the ventilation and blood flow goes to
compartments close to the normal V-Q ratio of about 1.0 and there is no blood flow to the unventilated compartment (shunt). Right: Patient with chronic
bronchitis & emphysema. Considerable blood flow is going to compartments with low V-Q ratios. Blood from these units will be poorly oxygenated and will
depress the PaO2. There is also excessive ventilation to lung units with high V-Q ratios. These units are inefficient at eliminating CO 2.

Differences in both alveolar ventilation and blood flow between the apex and the base can be explained in terms of gravity. At the apex because of ed gravity
the PIP es (opp. changes occur at the base resulting in the apex having large stiff alveoli & the base having small compliant alveoli). V/Q = 0.8 is the most
efficient lung unit. V/Q < 0.8 means that lung unit is under-ventilated & V/Q > 0.8 means that lung unit is over-ventilated (this will inturn lead to the gas
changes that you see above). Example: If the V/Q ratios of 2 lung units are 0.6 & 0.7 respectively both lung units are under-ventilated & will have a P O2 < 100
& PCO2 > 40. Low V/Q ratios are almost always associated with HPV decreasing blood flow in that lung unit and trying to e the V/Q closer to the
ideal of 0.8. HPV is designed to do this. The small amount of shunting that occurs in the normal lungs is seen mostly at the bases because of the low V/Q ratio
seen there. The apex of the lung has a small dead space component to it & the base of the lung has a small shunt component to it (this shunting is responsible
for the A-a gradient in the normal lung). A peanut blocking an airway will e V/Q & a thrombus blocking a pulmonary vessel will e the V/Q (in the occluded unit).
In severe exercise ventilation es more than perfusion V/Q es (more easier to move air than to move liquid).

ed V/Q Ratio

Lung Apex

Dead Space

Hypercapnia

ed V/Q Ratio

Lung Base

Shunting

Hypoxemia

e in alveolar perfusion resulting in a failure to eliminate CO2. This

mechanism cannot e the PaO2 within the unit.

e in alveolar ventilation resulting in a failure to deliver O 2 to the alveoli.

ed PCO2 may develop in that unit with large shunts.

Bold items indicate death and going to heaven subsequently. Think in terms of alveolar ventilation bringing atmospheric O 2 from outside into the alveolus & the
pulmonary blood flow bringing in CO 2 from the body into the alveolus (this explains the hypoxemia seen with a low V/Q & the hypercapnia seen with a high V/Q).
Airway obstruction (low V/Q regions or shunt) more hypoxemia than hypercapnia when compared to identical degrees of vascular obstruction (high V/Q
regions or dead space) relatively more hypercapnia than hypoxia. Note that in high V/Q regions it is the PACO2 that is ed. The PaCO2 actually es and an a-A
CO2 gradient exists indicating the presence of alveolar dead space. The PaCO2 > end-tidal CO2(PACO2). The CO2 is not delivered to the alveoli thus elevating the
PaCO2. When more than 60% of CO is shunted co-existing hypercapnia begins to develop even in shunts. If there is a huge dead space + no change in PaCO2
it just means pt. has ed his alveolar ventilation to get rid of the excess CO 2 through normal lung regions. The extent of V A/Q mismatch can be estimated by
measuring VD/VT (ratio of physiologic dead space to tidal volume) = see formulas. V D/VT is 0.20 - 0.35 in resting normal subjects (20% - 35% of the tidal volume
may be dead space). In patients with ed VA/Q it can be > 0.35 and can even be 0.50 i.e. half the ventilation is wasted. Another way of estimating VA/Q
mismatch is the A-a O2 gradient & the a-A CO 2 gradient. As the V/Q es (and a larger percent of CO is being shunted) supplemental O2 becomes less effective
in ing the PaO2. This situation is most commonly seen in ARDS.

Think this way:

[1] ed V/Q Dead Space over-ventilated ed PAO2 & ed PACO2. CO2 is not delivered to the alveoli for excretion Hypercapnia. Assuming that minute
ventilation remains constant, increasing the dead space automatically decreases alveolar ventilation and hence CO 2 excretion. In a patient with a large
pulmonary embolism, the end-expired PCO2 will be considerably lower than the PaCO2. In pulmonary embolism, many of the alveoli are unperfused, and
contribute no CO2 to the expired air.
[2] ed V/Q Shunt under-ventilated ed PAO2 & ed PACO2. Getting O2 into the lung is a problem Hypoxemia. Only low V/Q can give rise to hypoxemia.
Low V/Q regions will be associated with HPV. With a very large shunt you will also get hypercapnia. Shunt Examples: Diffuse alveolar filling / Collapse /
Consolidation / Abnormal arteriovenous channels / Intracardiac shunts.
Etiologies of Hypercapnia:

Pa

V
RR (V V )

[1] ed CO2 production (hypermetabolism): Fever, Seizures, Sepsis, Hyperalimentation, ed WOB, High Carb. diet + underlying lung disease (high RQ)
[2] ed RR (Central hypoventilation): Drugs, Brainstem lesions, Obesity-hypoventilation syndrome, stroke
[3] ed Tidal Volume: Skeletal muscle weakness, Impaired neuromuscular transmission (GBS / MG / Botulism / Muscular Dystrophy), Lung / chest wall
compliance, Airway obstruction (COPD, Asthma, Obstructive sleep apnea, Upper airway obstruction), Respiratory muscle fatigue
[4] ed Dead Space Volume: Excessive PEEP
Clinically significant hypercapnia is never caused by a diffusion defect.
Very low V/Q areas affect O2 more than CO2. Very high V/Q areas affect CO2 more than O2. This then creates an alveolar arterial difference for both the
gases.

DIFFUSION
Movement of gases through the conducting airways occurs by bulk flow (results from differences in
total pressure, and molecules of different gases move together along the total pressure gradient).
During diffusion, different gases each move according to their own individual partial pressure
gradients. By the time the air reaches the alveoli, bulk flow ceases (total cross-sectional area
increases velocity of the bulk flow decreases) , and further gas movement occurs by diffusion.
Oxygen then moves through the gas phase in the alveoli according to its own partial pressure
gradient. Henrys law = amount of a gas absorbed by a liquid is directly proportional to the partial
pressure of the gas to which the liquid is exposed and the solubility of the gas in the liquid. O2 must
diffuse through surfactant, the alveolar epithelium, the interstitium, and the capillary endothelium
plasma, where some remains dissolved and the majority enters the erythrocyte and combines
with Hb. Factors that determine the rate of diffusion of gas through the alveolarcapillary barrier is
given by Ficks law for Diffusion:

CO2 diffuses about 20 times more rapidly than does O2 through tissue sheets because it has a much
higher solubility but not a very different molecular weight. For this reason, patients develop
problems in oxygen diffusion through the alveolar-capillary barrier before carbon dioxide retention
due to diffusion impairment occurs.
Vgas = Volume of gas diffusing through the tissue barrier per time (mL/min)
A = surface area available (area of the blood-gas barrier = 70m2)
T = Thickness of the barrier or the diffusion distance. A & T are structural factors. The others are gas factors.
Structural factors will respond to supplemental O2, because by increasing the gradient, the transfer will increase.

D = Diffusion Coefficient (or) diffusivity of the particular gas in the barrier (Solubilty = main factor).
P1 - P2 = Partial pressure difference of the gas across the barrier
Exercise more capillaries are recruited available surface area es. If VR falls (hemorrhage) or if
PA is raised by +ve pressure ventilation capillaries derecruited available surface area es (also
with emphysema & aging). Barrier thickness es in interstitial fibrosis or interstitial edema.
Diffusion and Perfusion Limitations
RBC and its attendant plasma spend an average of about 0.75 seconds inside the pulmonary
capillaries at resting CO (0.25 seconds during severe exercise). Experiment considers the partial
pressure of both gases to be the same in the alveoli initially (that is just simultaneously inhaled).
The graph shows the rise in partial pressure of the 2 (CO & N2O) gases in the blood. Each gas will
act independently of the other. If the partial pressure of a gas in the plasma equilibrates with the
alveolar partial pressure of the gas within the amount of time the blood is in the pulmonary capillary,
its transfer is perfusion limited; if equilibration does not occur within the time the
blood is in the capillary, its transfer is diffusion limited.

Diffusion-Limited:
Capillary PCO rises very slowly and never (even closely) reaches alveolar PACO. Affinity of CO for Hb is
about 210 times that of oxygen for Hb. The CO that is chemically combined with Hb does not
contribute to the partial pressure of CO in the blood because it is no longer physically dissolved in it.
The partial pressure gradient across the alveolar-capillary barrier for CO is well maintained for the
entire time the blood spends in the pulmonary capillary, and the diffusion of CO is limited only by
diffusivity / surface area / thickness of the barrier. Note that the content of CO (in ml of CO per ml
of blood) if measured simultaneously, will be very high. CO transfer from the alveolus to the
pulmonary capillary blood is referred to as diffusion-limited.

pErfusion
limited =
Equilibrates
Diffusion
limited = Does
not equilibrate

Perfusion-Limited:
The partial pressure of N2O in the pulmonary capillary blood equilibrates very rapidly with the partial
pressure of N2O in the alveolus because it moves through the alveolar-capillary barrier easily and
dissolves in blood but does not combine chemically with the Hb. After only 0.15 seconds of exposure
the partial pressure gradient across the alveolar-capillary barrier has been abolished. From this point
on (last 0.65 seconds), no further N2O transfer occurs from the alveolus to that segment of the
blood that has already equilibrated. The transfer of N2O is therefore perfusion-limited. N2O transfer
can be ed by ing the amount of time the blood stays in the pulmonary capillary after equilibration
has occurred (i.e by ing CO). Note that increasing CO recruits previously unperfused capillaries &
the diffusion of both CO and N2O will e as the surface area for diffusion es.
Diffusion Of O2 : N2O illustrates how gas transfer is limited by blood flow; CO illustrates how gas transfer is limited by
diffusion. The profile for O2 falls between that for CO & N2O but is more like that of N2O (under normal conditions). The PO2
begins rising from 40 mmHg (the PO2 of mixed venous blood) & equilibration with the alveolar PO2 of about 100 mm Hg
occurs within 0.25 seconds (one third of the time the blood is in the pulmonary capillary) at normal resting CO. O2 moves
easily through the alveolar-capillary barrier and into the RBC, where it combines chemically with Hb. At normal P AO2, the
Hb becomes saturated with O2 very quickly (When Hb is getting saturated the O2 gradient continues to exist because O2
that is combining with Hb will not contribute to the PO2 of blood). As this happens, the PO2 in the capillary blood rises
rapidly to equal that in the alveolus, and from that point on, no further O2 transfer can occur. Therefore, under the
conditions of normal PAO2 & resting CO, O2 transfer from alveolus to pulmonary capillary is perfusion-limited.

Normal PAO2 : Mixed venous PO2 is 40 mmHg & PAO2 is 100 mmHg. With exercise blood moves through the
pulmonary capillary much more rapidly (blood stays in the capillary for only 0.25 seconds during severe
exercise). Total O2 transfer into capillary blood per time increases because there is no perfusion limitation of
O2 transfer (also because of recruitment of previously unperfused capillaries increases the surface area for
diffusion & because of better matching of ventilation and perfusion). Abnormal alveolar-capillary barrier
(fibrosis / interstitial edema) approach diffusion limitation at rest and have a serious diffusion limitation
during strenuous exercise. Grossly abnormal alveolar-capillary barrier diffusion limitation of O2 transfer
even at rest. Thus with vigorous exercise, there is still time to fully oxygenate the blood. Pulmonary endcapillary PO2 still equals alveolar PO2 (Equilibrates = pErfusion limited). In abnormal situations (thickening of
the alveolar-capillary membrane) O2 diffusion is impaired & end-capillary PO2 may not reach equilibrium with
alveolar PO2 (difference between alveolar and end-capillary PO2. Does not equilibrate = Diffusion limited).

Low PAO2: Mixed venous PO2 is 20 mmHg & PAO2 is 50 mmHg. Alveolar Hypoxia (high altitude or
inhaling a low O2 mixture) Decreased alveolar-capillary partial pressure gradient (es from 60 to
30 mmHg) blood PO2 takes longer to equilibrate with the alveolar PO2. Low PAO2 also sets the upper
limit for the end-capillary blood PO2. Because the O2 content of the arterial blood is decreased, the
mixed venous PO2 is also decreased. A normal person exerting himself at high altitude is subject to
diffusion limitation of O2 transfer.

Diffusion of CO2:
In a normal person with a mixed venous PCO2 of 45 mm Hg and an alveolar PCO2 of 40 mm Hg, an
equilibrium is reached in about 0.25 seconds [Inspite of a partial pressure gradient of only 5 mm Hg
(60 mm Hg for O2) CO2 still equilibrates within 0.25 seconds because diffusivity of CO2 is about 20
times that of O2]. CO2 transfer is therefore normally perfusion-limited, although it may be diffusionlimited in a person with an abnormal alveolar-capillary barrier.
Diffusing capacity of the Lung (DL):

The diffusing capacity is the rate (volume/min. V stands for Volume) at which O2 or CO is absorbed
from the alveolar gas into Hb within the pulmonary capillaries (in ml/min) per unit of partial pressure
gradient (in mmHg). Area (A), diffusivity (D), and membrane thickness (T) are combined into one
term, lung diffusing capacity (DL). Transfer of CO is limited solely by diffusion, and it is therefore the
gas of choice for measuring the diffusion properties of the lung (O2 not used because under some
circumstances diffusion limitation occurs). VCO = volume of CO taken up per time / P1 = PACO / P2 =
mean capillary PCO. The latter is too small and therefore neglected (affinity of CO for Hb is 210 times
greater than that of O2, which causes the PCO to remain essentially zero in the pulmonary capillaries).
Diffusing capacity of the lung for carbon monoxide (DLCO) is the volume of CO transferred in
ml/min/mmHg (of alveolar partial pressure).
Normal DL = 25 ml/min/mmHg. Increases to two or three times this value on exercise because of
recruitment and distension of pulmonary capillaries thus ing the available surface area for gas
exchange .

DL depends on: an equal contribution from below 2 factors:

(1) DM = Diffusion of O2 / CO through the Membrane (including the plasma & red cell interior)
(2) reaction rate of O2 / CO with Hb (q) & pulmonary capillary blood volume (VC). Also called
Transfer Factor to reflect the fact that it does not solely reflect the diffusion properties of the lung.
DLCO is ed with:
[1] Thickening of the barrier: interstitial / alveolar fibrosis (sarcoidosis / scleroderma / asbestosis
/ berylliosis / idiopathic fibrosis) or with conditions causing interstitial / alveolar edema.
[2] ed surface area: emphysema / tumors / low cardiac output / low pulmonary capillary blood
volume (ed PCBV derecruitment) / V-Q mismatch / pneumonectomy / space occupying lesions.
[3] ed uptake by erythrocytes: Anemia (ed Hct) / low pulmonary capillary blood volume (ed
Cardiac Output)
[4] V/Q Mismatch
Most common technique = Single-Breath Test (Reliable. Subject breathes a gas mixture containing a
low conc. of CO. The rate of disappearance of of CO from the gas mixture is proportional to DL). It is
possible to separately determine DM and Vc by measuring the diffusing capacity for CO at different
PO2 values (q for CO is reduced if a subject breathes a high 02 mixture because the O2 competes CO
for Hb).
Examples:
Supine Standing: pooling of blood in extremities VR RV Output derecruitment of
pulmonary capillaries ed surface area for diffusion slight e in DL.
Exercise: DL es. O2 transfer will also increase because at high cardiac outputs linear velocity of
the blood moving through the pulmonary capillaries increases less perfusion limitation of O2
transfer.
Valsalva: es pulmonary capillary blood volume es diffusing capacity
Emphysema: destroys the alveolar interstitium and blood vessels decreasing the surface area for
diffusion

Although the diffusing capacity may be influenced to some extent by the thickness of the alveolar-capillary membrane, it is most
dependent on the number of functioning alveolar-capillary units (surface area available for gas exchange) & volume of blood (hemoglobin)
in the pulmonary capillaries available to bind CO. Because diffusing capacity may be depressed if a patient is anemic, the observed value
is generally corrected for the patients hemoglobin level.
In practice, the diffusing capacity is commonly decreased in three categories of disease:
(1) Emphysema
(2) Interstitial Lung Disease (ILD)
(3) Pulmonary Vascular Disease
In disorders that affect only the airways and not pulmonary parenchymal tissue (asthma / CB), diffusing capacity is generally preserved.
The diffusing capacity is elevated in cases of recent intrapulmonary hemorrhage as a result of ed uptake of CO by Hb in the erythrocytes
within the alveolar spaces.
DLCO seen with:

ed recruitment of the pulmonary vascular bed (exercise / left to right intracardiac shunts)

asthma (increased pulmonary blood volumes due to more -ve intrathoracic pressure)

extremely high altitudes

early congestive heart failure

ed Hb (polycythemia / pulmonary hemorrhage)

DLCO seen with:

disruption of the alveolar-capillary surface

destruction of alveoli and adjacent capillary networks (emphysema)

alveolar filling with fluid or pus (pulmonary edema / pneumonia)

atelectasis (lung tumor)

ed tissue in the interstitial space (ILD). Although thickening of the alveolar-capillary interface (because of interstitial
inflammation and fibrosis) might be expected to be responsible for this decrease, it is not the major factor. Inflammation &
fibrosis destroy a portion of the alveolar-capillary interface and reduce the surface area available for gas exchange.

ed blood flow across ventilating alveoli (pulmonary embolism)

pulmonary hypertension - as a result of the hypertension itself & secondary to loss of the pulmonary vascular bed (occlusion of a
sufficient cross-sectional area of the pulmonary arteries by material within the vessels, such as pulmonary emboli)

DLCO is clinically most useful in distinguishing emphysema from asthma & CB or assessing interstitial lung disease.
Diffusing capacity tends to be decreased in patients who have loss of alveolar-capillary bed (as seen in emphysema) but not in
those without loss of available surface area for gas exchange (as in chronic bronchitis and asthma).

V CO =

D (P1 P2)

The partial pressure of CO in blood is 0 because all are present in combination with Hb (P 2 = 0). If alveolar partial pressure of CO is maintained at 1 mmHg
In a young healthy person with normal surface area (A) & membrane thickness(T), a 1 mmHg gradient of CO will produce a CO transfer of 25 ml/min. It
correlates well with the level of structural damage (D is a constant and therefore V CO A/T) and therefore is very useful when measured serially over time. ed
in emphysema & fibrosis but ed with exercise.

GAS TRANSPORT

O2 is transported both physically dissolved (2% of O2) in blood and chemically combined to Hb
(98% of O2).
Dissolved O2 (ml/dl) = 0.003 (ml/dl/mmHg) PO2 (mmHg). Direct linear relationship between
PO2 & dissolved O2.
Arterial blood with a PaO2 of 100 mmHg (at 37C) contains 0.3 mL of dissolved O2/100 mL of blood (0.3
vol%).
Blood O2 content is expressed in ml of O2 per 100 mL of blood, or volumes percent (vol%).
The O2 physically dissolved in the blood is totally insufficient to fulfill the bodys O2 demand (250ml
O2/min) even at rest.
Hb molecule can combine chemically with four O2 (or) CO molecules.
Each gm of Hb when fully saturated with oxygen, binds 1.34 mL of oxygen (1.34 ml O2/g Hb).
O2-carrying capacity (ml O2/dl) = 1.34 Hb conc. in gm/dl. The maximum amount of oxygen that
can be carried by Hb. A person with a Hb of 15 gm/dl has an O2-carrying capacity of 20.1 mL O2/dl
blood (or) 20 vol% (means 20 volumes of O2 per 100 volumes of blood).
The PO2 of plasma determines the amount of O2 that binds to Hb.
O2 concentration (or) O2 content (ml O2/dl) = (O2 bound to Hb + dissolved O2) = (1.34 Hb conc.
%Sat) + (0.003 PO2). %Sat = % Saturation of Hb (also called SO2)
O2 saturation is the ratio of the quantity of O2 actually bound to the quantity that can be potentially
bound. For example, if O2 content is 16 mL O2/dL blood and O2 capacity is 20 mL O2/dL blood, then the
blood is 80% saturated.
%Sat =
100

Oxyhemoglobin Dissociation Curve (ODC) = relationship between plasma PO2, O2 saturation, and
O2 content (3 closely related indices of oxygen transport) is illustrated by the ODC. Divided into a
plateau and steep region. For O2 content assume that the conc. of Hb is 15 gm/dl.
PaO2 decides O2 Saturation, which inturn decides O2 content
Not linear but S-shaped curve (steep at the lower PO2s and nearly flat at PO2s above 70 mmHg).
Mixed venous blood has a PO2 of 40 mmHg Hb is 75% saturated (SvO2; according to ODC).
Assuming a Hb conc. of 15 gm/dl O2 content = (1.34 15 0.75) + (0.003 40) = 15.08 + 0.12 =
15.2 ml O2/100ml blood.

Arterial Blood has a PO2 of 100 mmHg Hb is 97.5% saturated (SaO2; according to ODC). Assuming a
Hb conc. of 15 gm/dl O2 content = (1.34 15 0.975) + (0.003 100) = 19.57 + 0.3 = 19.87 ml
O2/100ml blood.
Thus, in passing through the lungs, each 100 mL of blood has loaded approx. 5 ml O2 assuming CO
of 5 L/min 250 ml of O2 is loaded into the blood per minute.
ODC plateau (PO2 >70mmHg) = loading phase (O2 is loaded onto Hb to form oxyHb in the pulmonary
capillaries). The plateau region shows how O2 saturation and content remain constant despite wide
fluctuations in alveolar PO2. e PaO2 from 100 to 120 mmHg Hb would become only slightly more
saturated (97% to 98%). For this reason, O2 content cannot be raised by hyperventilation. Even if the
PAO2 falls somewhat, loading of O2 will not be affected. At a PO2 of 70 mmHg Hb is still 94.1%
saturated O2 content is approx. 19 ml O2/dl (not bad at all).
This also shows that PO2 is a better diagnostic indicator of the status of a patients respiratory system
than is the arterial O2 content ( but the O2 content is more important physiologically to the patient).
RBC reaches systemic capillary exposed to lower PO2s O2 released by Hb. PO2 in the capillary
varies (very low in some tissues myocardium & higher in others kidney). The steep unloading
phase of the ODC allows large quantities of O2 to be released for a small e in PO2.
Picture. Adult ODC (37C / pH 7.40 / PCO2 40 mmHg). The P50 is the partial pressure of oxygen at
which Hb is 50% saturated with O2.
Temp. / pH / PCO2 / 2,3-BPG shift ODC to the right (for any particular PO2 there is less O2
chemically combined with Hb). All happen as blood enters metabolically active tissue. The effects of pH
/ PCO2 / temp. are more pronounced at lower PO2s ( unloading in the tissues). P50 es.
The influence of pH (and PCO2) on the ODC is referred to as the Bohr effect. High PCO2s in blood are
often associated with low pHs, therefore these two effects often occur together.
At very low blood temp., Hb has such a high affinity for O2 that it does not release the O2. O2 is more
soluble in water (plasma) at lower temp. dissolved fraction will e.
2,3-BPG is produced during chronic hypoxic conditions allowing more O2 to be released from Hb at a
particular PO2. Use of banked blood ed O2 unloading to the tissues.
P50 is the PO2 at which 50% of the Hb present in the blood is in the deoxy state and 50% is in the oxy
state.
At a temperature of 37C, a pH of 7.4, and a PCO2 of 40 mm Hg, normal P50 = 27 mm Hg. If the ODC is
shifted to the right, the P50 increases. If it is shifted to the left, the P50 decreases.

ODCs for arterial and venous blood. The venous curve is shifted to the right because the pH is lower
and the PCO2 and temp. are higher. The rightward shift results in a higher P50 for venous blood. a =
arterial point (PO2 = 100 mm Hg); v = mixed venous point (PO2 = 40 mm Hg).

Anemia: %sat (SaO2) & PaO2 = Normal. ed amount of Hb ed O2 carrying capacity of the blood
ed arterial O2 content. Use O2 content on the Y axis of the ODC instead of %sat. %sat is normal
because content and capacity are proportionally reduced. ODC curve moves down without a change in
shape.

CO: Prevents the loading of O2 into the blood in the lungs by taking up O2 binding sites on Hb reversibly
COHb (carboxyHb) & also interferes with the unloading of O2 at the tissues (by left shifting the ODC).
CO is colorless, odorless, tasteless and does not elicit reflex coughing or sneezing (undetectable). A
nonsmoker who lives in a rural area may have only about 1% carboxyhemoglobin; a smoker who lives
in an urban area may have 58% carboxyhemoglobin in the blood. When Hb is 50% saturated with CO
(carboxyhemoglobin), the oxygen content is reduced to about 10 ml/dl. PaO2 is normal (O2 gradient has
not changed). %sat & O2 content ed. Cyanosis masked by the bright cherry red color of blood when
CO binds with Hb. Brain is the first organ to be affected by lack of O2. Treat with 100% O2.
MetHb: nitrite poisoning / oxidant drugs / congenitally in pts. with HbM
HbF curve = similar to that of HbA without 2,3-BPG. O2 leaves Hb and binds to myoglobin or HbF.
Abnormal Hbs may have either ed or ed affinities for O2.
Artificial blood: Fluorocarbon Emulsions can carry more O2 than plasma but not as much as Hb.
Cyanosis: High conc. of deoxyHb in the arterial blood. Cyanosis occurs when more than 5gm/dl of Hb,
in arterial blood is in the deoxy state. bluish purple.
Useful "anchor" points: PO2 40 SO2 75% CO2 15ml; PO2 100 SO2 97% CO2 20ml

CO2 Transport

Carried as dissolved CO2 = 5% / combined to proteins = 5% / as bicarbonate = 90%

About 250ml of CO2 is produced by tissue metabolism each minute in a resting 70kg person.
CO2 is 20 times more soluble in plasma than O2.
Dissolved CO2 (ml/dl): 0.06 (ml/dl/mmHg) PCO2 (mmHg).
At a PaCO2 of 40 mmHg (arterial blood) 2.4 ml/dl (5% of CO2 content)
At a PaCO2 of 45 mmHg (venous blood) 2.7 ml/dl (little more than 5% of CO2 content)
Carbamino compounds (mostly carbamino Hb): CO2 bound to the terminal amine gp. of proteins
(usually Hb). H + released in the process. 5% of total CO2 content.
Bicarbonate: 90% of the CO2 transported by the blood is carried as bicarbonate ions. Carbonic
anhydrase is present in RBCs but not in plasma. H2CO3 = carbonic acid / HCO3- = bicarbonate ion.

The CO2 Dissociation Curve (CDC):

CDC for whole blood (37C) at different oxyHb saturations. a = arterial point; v = mixed venous point.
Note that oxygenated blood carries less CO2 for the same PCO2.
The relationship between whole blood CO2 content and PCO2 is linear.
DeoxyHb (reduced Hb) is a good acceptor of H+ ions released during the formation of bicarbonate &
carbamino compounds (better buffer than oxyHb at physiological pH). Responsible for the bohr &
haldane effects.
At the tissues - ed CO2 H+ (formed during the formation of bicarbonate ion & carbaminoHb) ODC
shifts to the right (HbO2 + H+ HbH + O2) and CDC shifts to the left (binding of H+ by deoxyHb allows
more CO2 to be transported as HCO3- & carbamino compounds) ed affinity for O2 & ed affinity for
CO2.
CDC changes with change in H+ is called the haldane effect (deoxyHb CDC shifts to the left;
oxyHb CDC shifts to the right). Allows the blood to load more CO2 at the tissues, where there is
more deoxyHb, and unload more CO2 in the lungs, where there is more oxyHb.
ODC changes with change in H+ is called the bohr effect.
Total CO2 content of venous blood (PCO2 of 45 mm Hg) = 53 ml CO2/dl. Total CO2 content of arterial
blood (PCO2 of 40 mm Hg) = 48 ml CO2/dl. Each 100 mL of blood passing through the lungs therefore
unloads 5 mL of CO2. Assuming CO of 5 L/min 250 ml of CO2 is unloaded per minute.

Figures: Typical O2 and CO2 dissociation curves plotted with the same scales. Note that the CO2 curve is more
steeper & more linear. Proportions of the total CO2 concentration in arterial blood (Dissolved / HCO3- /
Carbamino).

Example 1: e in Hb concentration from 15 g/100 mL blood to 12 g/100 mL blood.

The blood O2-carrying capacity will decrease from 20.1 to 16.08 mL O2/100 mL of blood
The PaO2 is not affected and so the O2 saturation of the Hb that is present is also unaffected
If PAO2 is 104 mm Hg, then the PaO2 is about 100 and Hb is 97.5% saturated
The CaO2 (excluding physically dissolved O2) is therefore ed from 19.59 to 15.67 mL O2/100 mL of blood.
Example 2: Hb conc. = 10 gm/100 mL of blood. Blood is 97.4% saturated with oxygen at a PaO2 of 100 mm
Hg. What is the pts CaO2, including physically dissolved O2.
O2 concentration (or) O2 content (ml O2/dl) = (O2 bound to Hb + dissolved O2) = (1.34 Hb conc.
%Sat) + (0.003 PO2) = 13.05 + 0.3 = 13.35 mL O2/100 mL of blood
Example 3: What is the approximate SO2 of a blood sample that contains 10 gm Hb/100 mL blood and has an
oxygen content of 10 mL O2 /100 mL blood (ignore physically dissolved O2).
O2 carrying capacity = 13.4 ml O2/100 ml. % sat = content / capacity = 10/13.4 = 75%
Respiratory Acidosis: The arterial PCO2 is normally kept at or near 40 mm Hg (normal range is 35 to
45 mmHg) by the mechanisms that regulate breathing. Any impairment of VA can cause respiratory acidosis.

Depression of the respiratory centers in the medulla: Anesthetics / Sedatives / Opiates / Brain stem
injury or disease / Severe hypercapnia / Severe hypoxia
Neuromuscular disorders: Spinal cord injury / Phrenic nerve injury / Poliomyelitis / ALS / GBS /
Botulism / tetanus / MG / curarelike drugs / Diseases affecting respiratory muscles (muscular
dystrophies / electrolyte disturbances)
Chest wall restriction: Kyphoscoliosis / morbid obesity
Lung restriction: Pulmonary fibrosis / Sarcoidosis / Pneumothorax / Pleural effusions
Parenchymal diseases: Pneumonia / Pulmonary edema
Airway obstruction: COPD / Upper airway obstruction / obstructive sleep apnea
Hypoventilation of a patient on a mechanical ventilator

Respiratory Alkalosis: Alveolar ventilation in excess of that needed to keep pace with body CO2 production
(hyperventilation) results in alveolar and arterial PCO2s below 35 mm Hg. Causes of respiratory alkalosis
include anything leading to hyperventilation.

Central nervous Sysyem: Anxiety / Hyperventilation syndrome (psychological dysfunction of unknown

cause episodes of hyperventilation) / Inflammation (encephalitis, meningitis) / Cerebrovascular
disease / Tumors
Drugs or hormones: Salicylates / Progesterone
Bacteremias & fever
Pulmonary diseases: Acute asthma / PE

Overventilation of a pt on a mechanical ventilator

Hypoxic stimulation of alveolar ventilation & ascent to high altitude (In this case the PaO2 will be ed)

Asthma: during the attack the patient has hypoxemia, hypocapnia, and respiratory alkalosis. It is only when
the attack is very severe (that the patient cant do the additional work of breathing) that hypercapnia and
respiratory acidosis occurs. Mechanism: Bronchial smooth muscle spasm / mucus secretion obstruct the
ventilation to some alveoli HPV insufficient to divert all of the mixed venous blood flow away from the poorly
ventilated alveoli R to L shunt Causes PaO2 to e & PaCO2 to e pt. es alveolar ventilation (if able to)
lungs will unload CO2 but cannot load O2 (will not get much O2 into alveoli supplied by obstructed airways,
nor will it get much more O2 into the blood of the unobstructed alveoli because of the shape of the ODC)
hypoxemia, hypocapnia, and respiratory alkalosis.
ed alveolar ventilation is because of:
[1] Irritant receptors in the airways stimulated
[2] Hypoxia caused by the shunt stimulates the arterial chemoreceptors
[3] Emotional component feeling of dyspnea
Respiratory Compensatory Mechanisms
[1] Usually the cause of respiratory acidosis / alkalosis is a dysfunction in the ventilatory control mechanism or
the breathing apparatus itself. Compensation in these conditions must therefore come from outside the
respiratory system.
[2] The respiratory compensatory mechanism can operate very rapidly (within minutes) to partially correct
metabolic acidosis / alkalosis by altering alveolar ventilation. metabolic acidosis (ed blood H+ concentration)
stimulates chemoreceptors es alveolar ventilation PaCO2 es pH es towards normal (complete
compensation does not occur). The respiratory compensation for metabolic alkalosis is to e alveolar
ventilation thus ing PaCO2.

The plateau of the ODC reflects the carrying capacity while the steep portion of the curve reflects the affinity of Hb for O2 (P50). ODC reflects a
love affair between Hb & O2. Stuff that shift the curve (right or left) will only change the steep portion of the curve (P 50), the carrying capacity remains
unchanged. Anemia or polycythemia will shift the plateau without changing the P50 (27 mmHg). CO does both (P50 ed & plateau depressed).

Whenever ODC is drawn to depict anemia or polycythemia the Y-axis has got to be O 2 content (O2 concentration), because the % saturation is

ABG is useless for CO poisoning (Inside the emergency room this guy is breathing 21% room air PaO2 will be normal). What you want to

normal in both conditions.

determine is the % saturation (done with a co-oximeter: gives the O2 & CO % saturations). Greater the CO poisoning lower the O2 % saturation.

With a ed 2-3 BPG (shift to the left) it is easy to load O 2 in the lungs (resulting in a complete saturation of Hb) but this O 2 will not be released to the

tissues thus starving them of O2.

A shift to the right just means ed affinity of Hb for O2, thus releasing more O2 and ing the local PO2 (within tisses).
th

rd

At a PO2 of 40mmHg the 4 O2 will leave Hb & enter plasma Hb becomes 75% saturated. At a PO2 of 27 mmHg (called the P50), the 3 O2 molecule

will leave Hb and Hb becomes 50% saturated.

O2 per gmHb is just a sophisticated way of saying % saturation.

About 90% of CO2 is carried as plasma bicarbonate.

Solubility: CO2 > O2 > CO

Affinity for Hb: CO > O2 > CO2 (exactly the reverse)
CO2 is the most soluble gas you will encounter in clinical medicine.

HYPOXIA
ed O2 (often specified where in the body for example: tissue hypoxia / alveolar hypoxia).
Tissue Hypoxia = PO2 in tissues. because of ed O2 Delivery (DO2= CO CaO2). brain cells and heart cells =
most susceptible to hypoxia. Tissue hypoxia can be a result of low PAO2, diffusion impairment, right-to-left
shunts, or ventilation-perfusion mismatch (hypoxic hypoxia); ed functional Hb (anemic hypoxia); low
blood flow (hypoperfusion hypoxia); or an inability of the mitochondria to use O2 (histotoxic hypoxia).
Hypoxic Hypoxia (Hypoxemia): ed PaO2 SaO2 ed CaO2 ed PvO2 & CvO2 (as O2 is extracted from the
already hypoxic arterial blood). Amount of O2 that will combine with Hb is mainly determined by the PaO2.
Order below is from more common to less common.
[1] V Q Mismatch: Low V/Q regions (regional hypoventilation) ed PaO2 / ed A-a gradient / ed O2
content (mechanism described below). High V/Q regions (regional hypoperfusion) do not by themselves lead
to arterial hypoxia but they cause relative overperfusion of other units regional low V/Q thereby ing
PaO2 & the O2 content & ing the A-a gradient. Latter is seen with pulmonary embolism (Hypoxia in the latter
can also be due to low cardiac outputs, called hypoperfusion hypoxia). Basic mechanism = e in venous
admixture. HPV & local airway responses help to minimize V-Q mismatching.

The lung units with a high V/Q add relatively little O2 to the blood [After Hb is saturated with O2 (on the flat
part of the ODC), ing PO2 does not significantly e the O2 content] and this blood cannot compensate for blood
with a low PO2 & low O2 content coming from Low V/Q units (a small amount of venous admixture can
dramatically lower PO2 and O2 content, because you are now on the steeper portion of the ODC). Therefore
mixed capillary blood has a lower O2 content than that from units with a normal V/Q. Therefore hypoxemia
resulting from V/Q inequality cannot be eliminated by increases in ventilation (owing to the

sigmoid shape of the O2 dissociation curve). PaCO2 is usually normal or even ed because whenever the
chemoreceptors sense a rising PCO2, there is an increase in ventilatory drive returning PaCO2 to normal
(facilitated by the linear shape of the CO2 dissociation curve). This is the most common cause of hypoxemia in
disease states. Hypoxemia due to V/Q mismatch can be corrected with low to moderate flow supplemental O2.
[2] Shunts: refers to a true RL shunt. Blood is shunting past totally unventilated alveoli. ed PaO2 / ed Aa gradient / ed O2 content. To differentiate from a V-Q mismatch use 100% O2 test. Arterial hypoxemia
caused by true shunts is not relieved by high FIO2s because the shunted blood does not come
into contact with the high levels of O2. The Hb of the unshunted blood is nearly completely saturated with
oxygen at a normal FIO2 of 0.21, and the small additional volume of O2 dissolved in the blood at high FIO2s
cannot make up for the low Hb saturation of the shunted blood. May not have ed PCO2 if they are able to
increase their alveolar ventilation (CO2 retained in the shunted blood stimulates increased alveolar ventilation)
or if they are mechanically ventilated. Right-to-left shunts cause extreme V/Q mismatch, with a V/Q ratio of
zero in some lung regions.
[3] Low PAO2: PAO2 determines the upper limit of PaO2. ed PAO2 ed PaO2. A-a O2 difference = Normal (to
differentiate this group from the other causes of hypoxemia: Low PaO2 + Normal A-a O2 gradient). ing FIO2 can
alleviate the alveolar and arterial hypoxia (in both hypoventilation and ascent to high altitude) but it cannot
reverse the hypercapnia of hypoventilation because ventilation is still depressed (in fact it may further
depress ventilation). ed PAO2 also impairs O2 diffusion by ing the O2 gradient from the alveolus to the
capillary.
[A] Hypoventilation (ed VA) leads to both alveolar hypoxia and hypercapnia (ed PaCO2 = Key Feature).
The ed PACO2 will further e PAO2 & PaO2. Easily identified by the presence of a PaCO2(pH) + PaO2. If PCO2 is
elevated and A-a O2 difference is normal, then hypoventilation is the exclusive cause of low PaO2. A small
e in supplemental O2 will correct the hypoxemia but mechanical ventilation is required to correct the
hypercapnia. If A-a O2 difference is elevated, then either V/Q mismatch or shunting also contributes to the
hypoxemia.
Causes are:

Depression of the respiratory centers in the brain (head injury / drug overdose / hypothyroidism /
chemoreceptor insensitivity)
Injury to the nerves supplying the respiratory muscles (spinal cord injury / poliomyelitis)
NMJ diseases (MG) & Muscular dystrophies
Altered mechanics of the lung or chest wall (noncompliant lungs due to sarcoidosis, reduced chest wall
mobility because of kyphoscoliosis or obesity); obesity hypoventilation (Pickwickian) syndrome
Airway obstruction (Emphysema)

[B] High altitudes (ed total barometric pressure encountered above sea level) & ed FIO2 (Fraction of
Inspired O2). PACO2 is ed because of the reflex increase in ventilation caused by hypoxic stimulation.
[4] Diffusion Block: Interstitial fibrosis & interstitial or alveolar edema. High FIO2s that increase the PAO2 to
very high levels may raise the PaO2 by increasing the partial pressure gradient for O2 diffusion. The A-a O2
difference is normal at rest but es with exercise (exercise-induced or exercise-exacerbated hypoxemia).
Rarely seen in the clinical setting. Severe pulmonary fibrosis during exercise / elite athletes during intense
exercise. In diseases like interstitial lung disease (ILD) diffusion limitation usually coexists with V/Q mismatch,
the latter playing a bigger role in causing hypoxemia (alveolar and/or interstitial inflammation & fibrosis
parenchymal destruction V/Q mismatch).
Approach to Hypoxemia: If a patient has a low PaO2, high PaCO2, and normal A-a O2 gradient, the cause of
hypoxemia is hypoventilation. If the PaO2 is low and the A-a O2 gradient is high, then the cause can be a
shunt, V-Q mismatch, or a diffusion block. Breathing 100% O2 will distinguish between V-Q mismatch & shunt.
Diffusion impairment is the least likely cause and diagnosed by elimination. Shunt may be caused by collapse
(atelectasis) / pus (pneumonia) / protein & fluid (ARDS) / water (CHF) / blood (hemorrhage).
Normal A-a O2 Difference = <15 mmHg
Hypoxemia = PaO2 < 85 mmHg

Cause of Hypoxemia

PAO2

PaO2

A-a O2 Difference

PACO2 & PaCO2

Increased FIO2
Helpful?

V-Q Mismatch

N/

Yes

R L Shunt

N/

NO (a)

Hypoventilation

Yes

ed FIO2

Yes

Diffusion Block

ed PaO2

ed SaO2

ed CaO2

ed PvO2

ed CvO2

N / (b)

Yes

(a) Only mild benefit secondary to ed dissolved O2

(b) es with exercise & normal at rest

Anemic Hypoxia: e in the amount of functioning hemoglobin (reduced ability of blood to carry O2). Example:
Methemoglobinemia / CO poisoning / ed or abnormal Hb or RBCs.
Hypoperfusion Hypoxia (or) Stagnant Hypoxia: low blood flow. locally (particular vascular bed) or
systemically (low CO shock). Circulatory Hypoxia.
Histotoxic Hypoxia: toxic substance that interferes with the ability of the tissues to utilize available O2
(Cyanide poisoning). Tissue edema or fibrosis may result in impaired diffusion of oxygen from the blood
to the tissues. O2 concentration of venous blood is high because of ed O2 consumption by the tissues.
Overutilization Hypoxia: delivery of oxygen to a tissue is completely normal, but the tissues metabolic
demands still exceed the supply and tissue hypoxia could result.
Cause of Hypoxia

PAO2 & PaO2

SaO2

CaO2

PvO2 & CvO2

Increased FIO2 Helpful?

Hypoxemia

ed PaO2

YES (a)

NO (b)

YES

NO (c)

(d)

NO

Anemic Hypoxia
CO Poisoning
Hypoperfusion Hypoxia
Histotoxic Hypoxia

Normal. A-a
O2 gradient
will also be
normal.

(a) Except for RL Shunts

(b) Mild benefit secondary to ed dissolved O2
(c) blood flowing to the tissues is already oxygenated normally what is needed is ed perfusion
(d) Venous PO2 and O2 content are ed because O2 is not utilized

The 3 steps in O2 use outlined above.

Arterial oxygen saturation (SaO2) = most commonly measured noninvasively by pulse oximetry, but can
also be measured by ABG
Reasonable to consider a resting SaO2 95% (or) PaO2 <80 mmHg as abnormal
For A-a gradient: PaO2 is measured by ABG, while PAO2 is calculated using the alveolar gas equation
The respiratory quotient is approximately 0.8 at steady state, but varies according to the relative
utilization of carbohydrate, protein, and fat.
The A-a gradient increases with higher FIO2. When a patient receives a high FIO2, both PAO2 and PaO2
increase. However, the PAO2 increases disproportionately, causing the A-a gradient to increase.
PaO2/FIO2 is a common measure of oxygenation. A normal PaO2/FIO2 ratio is 300 to 500 mmHg, with
values < 200 mmHg indicates severe hypoxemia. example: a pt whose PaO2 is 60 mmHg while
receiving an FIO2 of 0.50 (ie 50 percent) has a PaO2/FIO2 ratio of 120 mmHg.
V/Q mismatch is responsible for the normal A-a gradient
Normal CaO2 is approximately 20 mL O2/dL
Normal CvO2 is approximately 15 mL O2/dL. Mixed venous blood is drawn from the right atrium.
Peripheral venous blood tends to overestimate venous O2 content.
O2 delivery (DO2) is the rate at which O2 is transported from the lungs to the microcirculation. DO2 = CO
CaO2 = 1 L/min. CO can be measured by thermodilution using a pulmonary artery catheter, or
calculated using the Fick equation.
O2 consumption (VO2) is the rate at which O2 is removed from the blood for use by the tissues. Normal
VO2 in a conscious, resting person is approximately 250 mL O2/min.
O2 extraction: proportion of arterial oxygen that is removed from the blood as it passes through the
microcirculation. O2 Extraction Ratio = (CaO2 - CvO2)/CaO2. Normal = 0.25 (25%). DO2 and O2 extraction
are inversely proportional.
Changes in DO2 are balanced by reciprocal changes in oxygen extraction & therefore VO2 remains
constant. ed DO2 (heart failure) compensatory e in O2 extraction to maintain VO2.
When metabolic demand increases [exercise / pregnancy / critically ill patients (acute respiratory
distress syndrome / sepsis / septic shock)], VO2 increases to maintain aerobic cellular metabolism. This
is achieved by increasing both DO2 and O2 extraction.
ed O2 delivery or ed metabolic demand are common sequelae of medical illness.
Frank cyanosis does not develop until the level of deoxyHb reaches 5 g/dL (corresponds to an SaO2 of
67%).
In all causes of arterial hypoxemia, the tissues end up extracting all the O2 they can from this blood
thereby ing venous PO2. You cannot differentiate the specific cause by looking at systemic venous PO2.

Pulse Oximetry (SpO2): called the fifth vital sign. Pulse oximetry allows non-invasive measurement of arterial oxygen saturation

(SaO2) on an immediate or continuous basis (unlike blood gas analysis). Pulse oximetry offers the advantage of providing data on SaO2
(98 percent of arterial oxygen content), rather than PaO2 (remaining 2% dissolved in plasma). PaO2 can be used to estimate SaO2 & CaO2
(because the dissolved and Hb-bound O2 pools are in equilibrium) however several variables can alter the PaO2 SaO2 relationship.
Reasonable to consider a resting SaO2 95% (or) exercise desaturation of 5% as abnormal. Pulse oximetry is indicated in any setting
where hypoxemia may occur. Principle: Pulse oximetry uses the differential absorbance of light by oxyHb and deoxyHb to estimate the
SaO2 (uses 2 wavelengths of light to detect deoxyHb & oxyHb). Shines 2 beams of light one red (can see) and the other infrared (cannot
see). light travels from the light source to the detectors. Co-oximeters use 4 rather than 2 wavelengths of light to detect oxyHb,
deoxyHb, COHb, & metHb + they also require a sample of arterial whole blood.
Limitations:

Alveolar ventilation (or) PaCO2 not measured (do ABGs when alveolar hypoventilation is suspected).
Because it does not measure PaO2, it can delay detection of hypoxemia. A large decrease in PaO2 will not produce a significant fall
in SaO2 until the steep portion of the ODC is encountered at a PaO2 of 70 mmHg.

Results are signal-averaged over several seconds slight delay (is a problem when used for monitoring during intubation).

In premature neonates, pulse oximetry is unable to detect severe hyperoxemia ( O2 toxicity). Not good for severe
hyperoxemia (because of ODC shape: large changes in PaO2 may result in no change in SaO2 if the Hb is already 100%
saturated). Also not good for severe hypoxemia. Pts. at risk for severe hyperoxemia / severe hypoxemia ABG monitoring
should be included. Toxicity in premature neonates can be limited by titrating O2 to achieve an SaO2 of 90 percent (reflects a PaO2
of 60 mmHg).

Abnormal Hbs: CarboxyHb absorbs the same amount of light as does oxyHb (machine considers COHb & oxyHb to be the
same). CO poisoning falsely elevated reading. Dx. of CO poisoning: history & physical + elevated COHb level by co-oximetry of
a blood gas sample. Nonsmokers may have up to 3% COHb at baseline; smokers may have levels of 10 15%. Levels above
these values CO poisoning. MetHb: like above, SaO2 as measured by pulse oximetry is higher than the SaO2 calculated from

ABG analysis (= saturation gap). Fetal Hb gives values similar to those of adult Hb.
Hypoperfusion: accuracy es dramatically when SBP falls below 80 mmHg underestimation of the actual SaO2. Falsely low
(due to signal detection failure) in the setting of hemodynamic instability / poor limb perfusion (extremity elevation or
vasoconstriction). Use forehead sensors.

Hypothermia: False low value because of peripheral vasoconstriction. Use forehead sensors.

Anemia: An anemic patient with a Hb of 6 g/dL may have a low tissue oxygenation even if the pulse oximeter reads 99%.
Venous congestion: (tricuspid valve incompetence / cardiomyopathy) Falsely low SaO2 (due to generation of venous

pulsations. Instrument treats less oxygenated, pulsatile venous blood as part of the arterial sample).
Skin Pigmentation: Blacks / hyperbilirubinemia / nail polish [ mount probe on finger sideways. Red nail polish = no effect.

Vital dyes: Falsely low values (esp. methylene blue).

others (esp. blue) = falsely low values]. ed signal detection errors.

Sources of Artifact:

Improper probe placement: light from only one of the two light-emitting diodes may pass through the tissue. similar problem in
infants because of the small size of fingers (may result in differences in the path length of one light source compared to that of
the other).

Motion artifact: shivering / seizure.

Intense ambient light: false fixed low reading of 85%

Electromagnetic radiation: MRI scanners / cellular phones / electrocautery devices.

CONTROL OF BREATHING

Respiratory Centers:

The respiratory control system constitutes a negative-feedback system, with the PaCO2, pH, and PaO2 the
controlled variables. To act as a negative-feedback system, the central controller (DRG) must receive
information concerning the levels of the controlled variables from sensors (chemoreceptors) in the system.
3 centers in the pons / medulla. generates the rhythmic pattern of inspiration and expiration. Receive input
from various sources. Major output is to the phrenic nerve.
[1] Medullary Respiratory Center: DRG + VRG. Responsible for the basic rhythm.
DRG = in the NTS (nucleus of the tractus solitarius). inspiratory neurons. principal initiators of the activity of
the phrenic nerves. VRG = less important. expiratory neurons.
[2] aPneustic center: lower pons. Cut at 2 apneusis (prolonged inspiratory gasps followed by brief
expiratory efforts). excitatory effect on the DRG.
[3] Pneumotaxic Center (OR) PRG: upper pons. Terminates inspiratory effort and therefore regulates
inspired volume & secondarily RR.
Cut at 1: Normal
Cut at 2: Apneusis: Normally E > I, but here I > E (time).
Cut at 3: pattern maintained (although it is somewhat irregular)
Cut at 4: breathing ceases

Ataxic breathing Erratic rate and depth (DRG dysfunction). Only respiratory pattern with true localizing
value.
Hering-Breuer Inflation Reflex: Inflation stretch receptors CN 10 Medulla termination of
inspiration and initiation of expiration after a critical level of inflation has been reached prolongs expiratory
time es RR.

Pharyngeal Dilator Reflex: -ve pressure in the upper airway causes reflex contraction of the pharyngeal
dilator muscles keeping them open.
Irritant Receptors: noxious chemicals and particles CN 10 Medulla reflex constriction of bronchial
smooth muscle and an e in breathing rate.
J (Juxta-capillary) Receptors: located in the walls of the pulmonary capillaries & in the interstitium.
Pulmonary vascular congestion (Left heart failure) / ed interstitial fluid volume / Pulmonary Embolism J
receptors stimulated tachypnea (also responsible for the sensation of labored breathing).
Joint and muscle receptors: Mechanoreceptors located in the joints and muscles detect the movement of
limbs and instruct the inspiratory center to increase the breathing rate. Important in the early (anticipatory)
response to exercise.
Central Chemoreceptors:
The primary sensor for CO2 = Central Chemoreceptors (responds to the pH of brain ECF)
The bloodbrain barrier prevents the free movement of either H+ or HCO3 from blood to brain ECF,
whereas CO2 passes freely.
ed PaCO2 ed brain ECF PCO2 ed brain ECF pH (ed H+) ed pH at central chemoreceptor
Stimulation of central chemoreceptor Stimulation of DRG ed RR es PaCO2.
The goal of central chemoreceptors is to keep Paco2 within the normal range. PaCO2 is so precisely
controlled that it changes little (< 1 mm Hg) during exercise severe enough to increase metabolic CO2
production 10-fold.
CCs adapt within 12-24 hours (HCO3- is actively pumped into or out of the brain ECF)
Hypoxemia has nil effect on the CCs.
Peripheral (arterial) Chemoreceptors:
Carotid Body (CN9 / quantitatively more important) & Aortic Body (CN 10) chemoreceptors: Primary
sensors for O2. Respond to PaO2, PaCO2, and pH. Respond when Pao2 es to <60 mm Hg (not if PaO2 is
between 100 mm Hg and 60 mm Hg). They monitor PaO2 not O2 content (anemia will not stimulate the
arterial chemoreceptors).
Carotid body chemoreceptors also have a role in sensing PCO2 & pH (H+): less sensitive than CCs.
PCs do not adapt & are rapidly responding
Under normal resting conditions (PaO2 60 - 100 mmHg) the main drive for ventilation is PaCO2, acting
on CCs with a small contribution via (PaCO2 acting on) PCs.
When the PaO2 < 60 mmHg (dramatically reduced) the main drive for ventilation is low PaO2 stimulating
the PCs.
Severe exercise ( lactic acidosis) / Intrapulmonary shunts ( hypoxemia) / acute airway obstruction
( hypoxia and hypercapnia) all stimulate arterial chemoreceptors.
IMPORTANT:

Central = ed PCO2 (or) ed CSF pH.

Peripheral = PO2 < 60 / ed PCO2 / ed pH
What is regulated is alveolar ventilation (not total ventilation). V E is not precisely regulated. There are no central PO2 receptors. Example =
If you inhale a mixture of 10% O2 + 5% CO2 alveolar ventilation will e (stimulus being ed PaO2 acting on the peripheral receptors. 10%

O2 at sea level is only approx. half the normal amount).

Ventilatory CO2 response curves at three different levels of PaO2: PCO2s in the range of 38 to 50 mm Hg
increase alveolar ventilation linearly. The slope decreases with age. Hypoxia potentiates the ventilatory
response to CO2. At lower PaO2s the curve is shifted to the left and the slope is steeper (for any particular
PaCO2, the ventilatory response is greater at a lower PaO2).
Ventilatory response to PaCO2: Sleep (slow wave sleep) shifts the curve slightly to the right. A depressed
response to CO2 during sleep may be involved in central sleep apnea. Narcotics / Endorphins / anesthetics
depress the ventilatory response to CO2. With chronic hypercapnia, the ventilatory response PaCO2 is ed.
When CO2 retention persists for days, the kidneys compensate for the more acidic pH by excreting less
bicarbonate, and the levels of bicarbonate rises in both plasma and brain ECF. The elevated bicarbonate level
can buffer any acute changes in PCO2 the brain ECF pH value changes less for any given increment in PCO2.
Ventilation increases nearly linearly with changes in H+ concentration. Metabolic acidosis results in
hyperpnea coming almost entirely from the peripheral chemoreceptors (H+ crosses the BBB too slowly to affect
the central chemoreceptors).
Ventilatory responses to hypoxia at three different levels of arterial PCO2: At a normal PaCO2 of 38 to 40
mm Hg, there is very little increase in ventilation until the Pa O2 falls below 60 mm Hg. Response to hypoxia is
potentiated at higher PaCO2s. Response to hypoxia is related to the change in Pa O2 rather than the change in O2
content (anemia does not stimulate ventilation because the PaO2 is normal).

The increases in alveolar ventilation in response to increases in PaCO2 and H+ concentrations are nearly linear
within their normal ranges; the increase in alveolar ventilation in response to decreases in PaO2 is small near
the normal range and very large when the PaO2 falls below 60 mmHg.

Voluntary apnea for 90 seconds: PAO2 es & PACO2es PaO2 es & PaCO2es (ed H+) stimulate the arterial
chemoreceptors. Ninety seconds is enough for CO2 to diffuse across BBB and stimulate the central
chemoreceptors. The central chemoreceptors are not responsive to hypoxia. H+ will not cross the BBB in 90
seconds.

Apneustic center promotes prolonged inspirations. Pneumotaxic center inhibits the apneustic center thereby
terminating inspiration. If connection between both severed apneustic breathing. Cortex (higher centers)
adds a voluntary component and lesions above the pons eliminate voluntary control, but basic breathing
pattern remains intact.

RESPIRATORY SYSTEM UNDER STRESS

EXERCISE

Stresses the RS by ing CO2 production and ing O2 consumption.

O2 consumption (VO2) es (from 300 ml/min to 3000 ml/min; can e upto 6000 ml/min in an elite
athlete) linearly with ing work rate until VO2max is reached. An increase in work rate above VO2max can be
reached only via anaerobic glycolysis. The V stands for Volume.

Fick Equation:
O2 consumption/min = flow/min a-v O2 difference. VO2 is ed because of both an e in CO and a rise in
a-v O2 difference (ed O2 extraction e in the O2 concentration of mixed venous blood).
CO2 output es (from 240 ml/min to 3000 ml/min)
Respiratory Exchange Ratio (RER) = volume of CO2 produced / volume of O2 consumed.
RER es from about 0.8 (at rest, 240/300) to 1.0 (3000/3000) on exercise. This increase reflects a
greater reliance on carbohydrate (during exercise) rather than fat (at rest) to produce the required
energy. RER can also be >1 because of ed lactic acid buffering of H+ by HCO3- ed production of
CO2 (in addition to that derived from aerobic metabolism).

Breathing mechanics:
Elastic work of breathing ed: High lung volumes ed work necessary to overcome the elastic recoil of
the lungs and chest wall during inspiration (lungs are less compliant at higher lung volumes & the elastic
recoil of the chest wall is inward at high thoracic volumes).
Resistance work of breathing ed: ed turbulence (ed airflow rate) & dynamic compression (during
active expiration) ed resistance work.
Control of Breathing:
Ventilation es linearly with O2 consumption but begins to rise more rapidly when lactate starts
accumulating (called the Anaerobic Threshold) because H+ will stimulate the PCs directly. Unfit subjects
produce lactate at lower work levels when compared to well-trained subjects.
Mechanisms by which exercise increases minute ventilation: neural input from higher centers /
proprioceptors in joints and muscles / although mean values of PaO2 and PaCO2 do not change,
oscillations occur / K+ stimulating the arterial chemoreceptors / when AT is crossed: ed lactic acid
ed CO2 production.
Alveolar Ventilation:
e in minute ventilation (result of e in both VT and RR). Initially, the VT increases more than RR, but as
metabolic acidosis develops, the increase in RR predominates.
Lung Volumes: Increase in VT occurs at the expense of the IRV, with the ERV less affected. An e in the
blood volume (caused by ed VR) may e the TLC & VC slightly. FRC & RV unchanged.

e in physiologic dead space = anatomic dead space es (because of airway distention at high lung
volumes) + alveolar dead space es (as CO es).
PaO2 no change. PaCO2 no change until anaerobic metabolism sets in lactic acid H+ stimulate
alveolar ventilation PaCO2 es with severe exercise
Regional differences in alveolar ventilation seen in upright lungs attenuated
PvCO2 es (is coming from sk. muscle). this extra CO2 is expired by the lungs and never reaches
systemic arterial blood.
Pulmonary Blood Flow:
CO increases linearly with work level as a result of increases in both HR and SV. However, the change in
CO is only about a quarter of the increase in ventilation (it is much easier to move air than to move
blood). It is the CVS rather than the RS that is the limiting factor in exercise.
ed VR (due to deeper inspiratory efforts + extravascular compression by the exercising sk. muscle +
decrease in venous capacitance) contributes to the increase in CO.
ed CO ed pulmonary artery and pulmonary venous pressures recruitment /distension of
pulmonary capillaries (primarily in upper regions of the lung) mean PVR falls / regional differences in
flow attenuated more homogeneous V-Q ratios / greater surface area for diffusion.
MPAP es slightly (increase is not as great as the increase in pulmonary blood flow because of a
decrease in PVR).
V-Q Relationships
ed perfusion of upper regions of the lung improved matching of ventilation & perfusion
In severe exercise ventilation es more than perfusion V/Q es to between 2.0 & 4.0
In elite athletes at very high work levels there may be a e in PaO2 and e in the (A-a)DO2 (upto 30
mmHg) because of the following reasons:
o PVO2 es
o O2 transfer becomes diffusion limited (because linear velocity of blood flow es)
o mild interstitial pulmonary edema (ed pressure causes fluid to move out of the pulmonary
capillaries)
o ed PAO2 (because of ed V/Q)

Diffusion:
DLCO: es 3 fold, because of:
recruitment and distension of pulmonary capillaries, particularly in the upper parts of the lung es
surface area ed diffusing capacity of the membrane (DM)
CO (ed pulmonary blood flow) ed volume of blood in the pulmonary capillaries (VC)
Increased linear velocity of blood flow es the perfusion limitation on O2 transfer. ed blood flow
velocities may increase the possibility of diffusion limitation of gas transfer.
ed partial pressure gradient (PvO2 is lower and PvCO2 is higher than at rest).
O2 & CO2 Transport:
ed O2 unloading in tissues because of a right shifted ODC (ed P50) (because of ed PCO2 / H+ / Temp / 2-3
BPG) & ed muscle PO2. ed CO2 loading in tissues because of a left shifted CDC (because of ed deoxyHb).
Acid-Base: severe exercise anaerobic metabolism (AT) ed lactic acid metabolic acidosis.
The net result is that the PaO2, PaCO2, and pH are little affected by moderate exercise.
At very high work levels, PaCO2 es / PaO2 es / and pH es (lactic acidosis).

Variable
V O2 & V CO2
VE & VA

VT
RR
Physiological Dead Space
Pulmonary Blood Flow
Upper Lung Perfusion
PVR
V/Q ratio
Partial Pressure Gradient
PAO2
PaO2
PaCO2
pH
a-v O2 Difference
PvCO2
RER (VCO2/VO2)
MPAP
DLCO

Moderate

Severe

(2-4)

1.0

>1.0
Small

Training Effects: Most of the changes that occur as a result of physical training are because of alterations in
the CVS (ed ability to deliver O2) and in muscle metabolism (ed ability to extract the delivered O2) rather than
changes in the respiratory system. Cardiac Output is the limiting factor in exercise.
HIGH ALTITUDE:

At any altitude: PIO2 = 0.21 (PB 47).

PB at 19,000 ft is that of sea-level. PIO2 = [0.21 (380-47)] = 70 mmHg.
Hypoxic stimulation of the arterial chemoreceptors es alveolar ventilation PACO2 falls helpful in ing PAO2
& PaO2. Typically PaCO2, in permanent residents at 15,000 ft is about 33 mmHg.
At 20,000 ft PIO2 = 0.21 (350 47) = 64 mmHg
At 15,000 ft PAO2 = 0.21 (430 47) 33/1 = 80 - 33 = 47 mmHg.

Acute Effects:
Ascending rapidly to ed hts (acute mountain sickness) / cabin press. lost in an airplane no time for
acclimatization acute effects (symptoms are mainly due to hypoxia / hypocapnia / respiratory alkalosis /
cerebral edema). Sxs abate when the adaptive responses are established.
ed PAO2 & PaO2 stimulate the arterial chemoreceptors ed alveolar ventilation hypocapnia &
respiratory alkalosis. Resp. alkalosis shifts the ODC to the left initially.
The main drive for ventilation changes from CO2 on the central chemoreceptors at sea level to low PO2
drive of the peripheral chemoreceptors.
ing the climber's ventilation reduces the climber's PACO2 allowing the climber to raise his PAO2.
The ed rate and depth of breathing increases the WOB. Resistance work es because of
o active expiration dynamic airway compression.
o arterial hypoxemia reflex bronchoconstriction.
More uniform regional distribution of alveolar ventilation because of deeper inspirations
Alveolar hypoxia Generalized HPV ed pulmonary arterial pressure ed work done by right heart
hypertrophy of right heart. The hypertension is exaggerated by the polycythemia (ed viscosity of the
blood). Pulmonary hypertension rarely may lead to high-altitude pulmonary edema (HAPE)
(arteriolar vasoconstriction is uneven, and leakage occurs in unprotected, damaged capillaries =
capillary stress failure). Edema fluid has a high protein concentration (indicating that the permeability of
the capillaries is ed).
Acute mountain sickness (AMS) & high altitude cerebral edema (HACE) = AMS/HACE represents
a continuum, and AMS can progress to fatal HACE. Balance between hypocapnia (cerebral
vasoconstrictor) & hypoxia (cerebral vasodilation).
AMS: CNS symptoms (headache / nausea / insomnia) are because of cerebral hypoperfusion (because
of hypocapnia) & alkalosis. Disappears within 3 days.
HACE: Hypoxia (direct effect on cerebral vessels) cerebral vasodilation hyperperfusion and
distention of cerebral vessels edema ed ICP.
Acetazolamide (carbonic anhydrase inhibitor) can prevent the symptoms of AMS. es reabsorption of
bicarbonate by the proximal tubule of the kidney mild compensatory metabolic acidosis offsets the
respiratory alkalosis caused by hyperventilation. Also a diuretic es fluid retention & edema. No effect
on ed PaO2 / ed %Sat / hyperventilation.
Acclimatization

The most important feature of acclimatization to high altitude is hyperventilation ( respiratory

alkalosis). Other important features : Polycythemia / ed 2-3 BPG ( right shifted ODC) / HPV.
Renal compensation for respiratory alkalosis begins within a day: Renal excretion of HCO3- (augmented
by acetazolamide).
HCO3- leaves the CSF, and the pH of the CSF decreases toward normal
Within 3 to 5 days, new RBCs are produced, ing the hct and the O2-carrying capacity. Thus, although
the PaO2 is not ed, CaO2 es because of the ed blood Hb concentration (at the cost of ed blood
viscosity and ventricular workload).
The polycythemia also tends to maintain the PO2 of mixed venous blood (very close to sea-level values).
Inspite of ed % saturation, the total O2 content is normal and therefore the PvO2 is near normal.
Hypoxemia EPO from the kidney stimulates the BM Polycythemia
Hypoxemia ed concentrations of 2,3-BPG ODC shifted to the right (ed P50) Hb has ed affinity
for O2 ed O2 unloading in tissues
Hypoxemia (PaO2 < 60 mmHg) stimulation of the arterial chemoreceptors (persists indefinitely) ed
PaCO2 e in arterial pH (respiratory alkalosis)
HPV and pulmonary hypertension persist (along with increased blood viscosity), leading to RV
hypertrophy and chronic cor pulmonale (RV failure secondary to pulmonary hypertension). HPV is not
beneficial.
Cellular changes include ed myoglobin / ed no. of capillaries / ed no. of mitochondria (all these
changes e the ability of tissues to utilize the delivered O2).

At sea level: PAO2 = 150 40/0.8 = 100 mmHg

Altitude where PIO2 is 100 mmHg (but without a change in VA) = 100 40/0.8 = 50 mmHg (severe hypoxia)
Altitude where PIO2 is 100 mmHg (but with a doubling of VA) = 100 20/0.8 = 75 mmHg (hyperventilation is therefore a powerful
process in mitigating the hypoxia of high altitude)
Acute = Immediate; 72 hrs = early adaptive; 2 6 wks = late adaptive. Acutely the ODC is left shifted (because of the respiratory alkalosis); with adaptation
it shifts to the right (because of ed 2-3 BPG). CaO2 is acutely low because of ed % Sat, but then in normalizes because of ing Hb conc. This is one of the

situations when pH compensation is complete (comes down to 7.4) because of renal compensation (dumping of bicarbonate in urine). Changes in pH & Hb
explain most of the adaptations that occur over time. During adaptation urine pH is ed (because of bicarbonate dumping).

Variable

PAO2 & PaO2

Hb % Sat
PACO2 & PaCO2

Acute

72h (3 days)

2 to 6 wks

Arterial pH

Arterial

HCO3-

CSF pH
CSF
V A

HCO3-

RR

PVR (HPV)

MPAP

AMS / HACE

Hb Conc. & Hct.

VT

2-3 BPG
ODC P50
Erythropoietin

CaO2

PvO2

near normal

near normal

DIVING
Principles: The pressure at the bottom of a column of liquid is proportional to the height of the column, the
density of the liquid, and gravity. For each 33 ft of seawater (or 34 ft of fresh water) ambient pressure
increases by 1 atmosphere (atm): at a depth of 33 ft of seawater, total ambient pressure is equal to 1520 mm
Hg. The tissues of the body are composed mainly of water and are therefore nearly incompressible, but gases
are compressible and follow Boyles law. In a breath-hold dive (scuba diver who is not breathing) the volume of
gas in the lungs is inversely proportional to the depth attained. At 33 ft of depth (2 atm) lung volume is cut in
half; at 66 ft (3 atm) it is one third the original lung volume. As gases are compressed, their densities increase.
As the total pressure increases, the partial pressures of the constituent gases also increase, according to
Daltons law. As the partial pressures of gases increase, the amounts dissolved in the tissues of the body
increase, according to Henrys law. 1m = 3.3ft. The major stresses involved in diving include
elevated ambient pressure
decreased effects of gravity
altered respiration
hypothermia
The severity depends on the depth attained, the length of the dive, and whether the breath is held or a
breathing apparatus is used.
SCUBA (Self-Contained Underwater Breathing Apparatus) Diving:
The physiologic stresses on the respiratory system during scuba diving are mainly because of ed gas densities
and partial pressures. At ed depths gas density es resistance work of breathing es. Replace N2 with
helium for deep dives. Helium is only about 1/7th as dense as N2.
Barotrauma: If a closed cavity containing gas such as the lung, middle ear (with a clogged eustachian tube),
or intracranial sinus is exposed to high or low ambient (surrounding) pressures, the pressure difference may
cause compression on descent or overexpansion on ascent. Boyles Law = as pressure decreases, volume
increases. Barotrauma of ascent: Important for scuba divers to exhale as they ascend. If a diver does not
exhale while ascending, expanding pulmonary gas may overdistend and rupture the lung (burst lung)
hemorrhage / pneumothorax / air embolism. Not inhaling is also a problem (ascent ambient pressure falls
rapidly lung volume es alveolar gas partial pressures decrease PAO2 PaO2 lose consciousness,
called shallow water blackout). Gases trapped in the GIT may cause abdominal discomfort and eructation or
flatus as they expand. Barotrauma of descent is called squeeze. Lungs pulmonary congestion / edema /
hemorrhage.
Decompression Illness:
Arterial gas embolism is a likely consequence of an ascending diver neglecting to exhale upon rapid ascent.
Expanding alveoli rupture gas bubbles enter pulmonary capillaries carried into arterial blood cerebral
blood vessels paralysis.
Decompression sickness bubbles form in tissues of the body. Increasing ambient pressure causes an
elevation of the partial pressure of N2 in the body (N2 is very insoluble in body tissues at sea level). The high
partial pressure of N2 causes this normally poorly soluble gas to dissolve in the body tissues / fluids & especially
in body fat, which has a relatively high N2 solubility. At great depths, body tissues become supersaturated with
N2 (but this equilibration of N2 between the tissues and the environment needs time). During a fast ascent
(after a prolonged dive), ambient pressure falls rapidly and N2 comes out of solution, forming bubbles in body
tissues and fluids. Henrys Law = Solubility of a gas is directly proportional to the partial pressure of that gas
over the solution. The effect is the same as opening a bottle of a carbonated beverage. During the production of
a carbonated beverage it is exposed to higher than atmospheric pressures of gases, mainly carbon dioxide, and
then capped. The total pressure in the gas layer above the liquid remains greater than atmospheric pressure.
The partial pressures of gases dissolved in the liquid phase are in equilibrium with the partial pressures in the
gas phase. Gases dissolve in the liquid phase according to Henrys law. When the bottle is uncapped, the
pressure in the gas phase drops suddenly solubility of the gas in solution will e the gas dissolved in the
liquid phase comes out of solution, as a steady stream of bubbles.
Bubbles enter the venous blood & are usually trapped in the pulmonary circulation and rarely cause
the chokes (substernal chest pain, dyspnea, cough, pulmonary hypertension, pulmonary edema, and
hypoxemia) = extremely dangerous form of decompression illness
Can be carried from the venous blood to the arterial side through a PFO or an intrapulmonary shunt.
Bubbles that form in the joints of the limbs cause pain (the bends) or joint osteonecrosis.
Gas bubbles are perceived by the body as foreign inflammatory responses.

Treatment of Decompression Illness: Immediate re-compression in a hyperbaric chamber (forces the bubbles
back into solution), followed by slow decompression. Decompression illness may be prevented by slow ascents
from great depths and by substituting helium for N2 in inspired gas mixtures. Helium is only about half as
soluble as N2 in body tissues. Divers who ascend with no immediate effects of decompression may subsequently
suffer decompression illness if they ride in an airplane within a few hours of the dive. Commercial airplanes
normally maintain cabin pressures well below 760 mm Hg (corresponding to altitudes of 5000 to 8000 ft above
sea level).
N2 Narcosis: Most serious problems in diving arise when divers descend to depths in excess of 100 feet. The
total pressure at depths greater than 100 feet can cause problems such as N2 narcosis and O2 toxicity. At a
depth of 100 feet, the total pressure of air delivered to the diver is about 4 atmospheres. This results from a
water pressure of 3 atmospheres plus the surface air pressure of 1 atmosphere. The partial pressure of N2 at
this depth would be about 3.2 atmospheres. N2 at this pressure produces an anesthetizing effect similar to
nitrous oxide (laughing gas) N2 intoxication with loss of judgment, a state of euphoria, drowsiness, and
impaired judgment. If N2 narcosis develops, it can be quickly reversed by moving to a shallower depth. To
prevent N2 narcosis, deep divers use a mixture of helium + O2, + N2. Helium is not taken up by or liberated
from pulmonary capillary blood & like N2 is inert.
O2 Toxicity: The deeper a diver descends, the greater the partial pressure of O2. At a depth of 130 feet, the
total pressure is close to 5 atmospheres and the partial pressure of O2 will be close to 1 atmosphere (21% 5
atmospheres). Breathing compressed air at 130 feet is like breathing pure O2 at the surface only a problem if
done for several hours (O2 toxicity). When the partial pressure of O2 approaches 2 atmospheres, it may take
only several minutes for symptoms of O2 toxicity to appear. To prevent O2 toxicity, divers use a lower
percentage of O2 for deep dives. For example, a diver at 200 feet might breathe from a tank that contains only
4% O2.
High-Pressure Nervous Syndrome (HPNS): occurs when N2 has been replaced by helium to decrease gas
density, prevent N2 narcosis, and help avoid decompression sickness. Small amounts of N2 added to the
inspired gas mixture helps counteract this problem. May result from alterations in cerebral neurotransmission.
O2 Toxicity: 100% O2 at atmospheric pressure for 24 hours absorption atelectasis (substernal distress aggravated by deep breathing &
ed VC).

Suppose that an airway is obstructed by mucus The total pressure in the trapped gas is close to 760 mm Hg. Sum of the partial
pressures in the venous blood is far less than 760 mm Hg if pure O2 is breathed (because N2 is not contributing here and because of the
shape of the ODC the increase in venous PO2 is only about 15 mmHg) gas diffuses into the blood rapidly collapse of the alveoli occurs.
Reopening such an atelectatic area may be difficult because of surface tension effects. Absorption collapse also occurs in a blocked region
even when air is breathed, although here the process is slower. N2 has a low solubility therefore acts as a splint supporting the alveoli
and delaying collapse (splinting effect). Postoperative atelectasis is a common problem in patients who are treated with high O2 mixtures.
Collapse is particularly likely to occur at the bottom of the lung, where the alveoli are least well expanded or the small airways are closed &
also because retained secretions are more likely to collect at the lung base. This same basic mechanism of absorption is responsible for the
gradual disappearance of a pneumothorax, or a gas pocket introduced under the skin. Any lung unit with a low V/Q is more likely to
collapse when 100% O2 is inhaled (because all O2 is transferred into the blood and the splinting effect of low solubilty N2 is absent). Stated
differently low V/Q areas are converted to shunts). When more gas is removed from the lung unit than is inspired there will be atelectasis
of that lung unit. This is more likely to happen at the lung base where V/Q ratios are lower. Bottom line: Absorption atelectasis (secondary
to airway occlusion) & atelectasis (in low V/Q lung regions) are more likely to occur when the inspired O2 concentration approaches 100%.
This will inturn increase shunt flow and decrease PaO2. Use high inhaled O2 just enough to raise PaO2 to comfortable levels.

Other problems:

Pathological changes are seen in the pulmonary capillary endothelial cells (Free Radical Injury) Pulmonary Edema

Impaired gas exchange

Premature infants blindness (retrolental fibroplasia - fibrous tissue formation behind the lens). Because of local vasoconstriction
caused by high PaO2 (avoided if the PaO2 is kept below 140 mm Hg).
With SCUBA Diving: PaO2 can exceed 760 mmHg! At a PO2 of 4 atmospheres, convulsions occur within 30 minutes. For increasingly
deep dives, the O2 concentration is progressively reduced.

Hyperbaric O2 Therapy: ing the PIO2 to 3 atmospheres in special chambers the amount of dissolved O2 in
arterial blood can be increased to about 6 ml/100 ml (because the relationship is linear) needs of the tissues
can be met without functioning Hb. Fire explosions are serious hazards of a 100% O2 atmosphere, especially at
ed pressure (for this reason, O2 in a pressure chamber is given by mask, and the chamber itself is filled with
air). Uses: severe CO poisoning / gas gangrene (organism cannot live in an high O2 environment) /
decompression sickness.
Liquid Breathing: Possible to survive for some hours breathing liquid (fluorocarbon exposed to 100% O2 at 1
atmosphere. Fluorocarbon has a high solubility for O2 and CO2) instead of air. ed density and viscosity than air
work of breathing ed. Adequate PaO2 can be obtained if the inspired concentration is raised sufficiently. A
serious problem is eliminating CO2 (diffusion rates of gases in liquid are much slower CO2 retension &
acidosis). The diffusion pressure of O2 can always be raised by increasing the PIO2, but this option is not
available to help eliminate CO2.
Immersion up to Neck: Effects are mainly because of e in pressure (20 cm H2O) outside the thorax,
abdomen, and limbs. Used as a model of weightlessness for training astronauts.
1) Hydrostatic pressure of neck-deep water es the outward elastic recoil of the chest wall es FRC &
es the WOB. FRC es at the expense of ERV.
2) Max ve PIP that can be generated = -100 cm H20 cannot descend to below 3.3ft (100 cm or 1m)
breathing surface air. At a depth of 300 cm there will be a press. of 300 cmH2O outside the thorax.
The only way to go deeper is to hold your breath (or) by using SCUBA.
3) ed pooling of venous blood in gravity-dependent regions ed central blood volume SV & CO
ed pulmonary blood flow / volume recruitment ed DL & better V-Q matching.
4) Immersion diuresis (stimulation of stretch receptors in the LA ed ADH & ed ANP release
dehydration)
5) Natriuresis & kaliuresis
6) Hemodilution: Loss of gravity ed hydrostatic pressure in the dependent veins Interstitial fluid
shifted into intravascular space. ed Hct.
Some of the same changes occur with space flight: 3 / 4 / 6 / Postural hypotension occurs on return to earth /
osteoporosis / muscle atrophy / absence of sedimentation (with inhaled aerosol).
Diving Reflex: Face immersion (especially into cold water) Receptors in nasal mucosa & face
1) Apnea
2) HR
3) SVR es perfusion to all organs except to the strongest autoregulators (heart & brain)
4) Splenic contraction releases stored RBCs ed O2 carrying capacity ed O2 content at the same PaO2
Important Concepts:
1)
2)

3)

The main stresses of exercise are ed O2 demand and ed removal of CO2 and H ions; Exercise is limited by the CVS & not by the RS.
The main physiologic stresses of altitude are hypoxia and secondary hypocapnia and respiratory alkalosis; acclimatization occurs mainly by renal
compensation for the respiratory alkalosis, erythropoiesis, elevated 2,3-BPG concentrations, and resolution of cerebral edema.
The main physiologic stresses of diving are caused by ed ambient pressures causing gas compression, leading to ed partial pressures & densities
of gases.

4)

Density of inspired gas Resistance to gas flow (deep sea diving)

5)

Density of inspired gas Resistance to gas flow (breathing helium)

GAS LAWS
A gas consists of small particles (individual atoms or molecules) moving around randomly. The total volume of gas particles is so small compared
to the total volume of gas. This means that a gas consists almost entirely of empty space. A gas expands to fill the volume of its container. This
characteristic allows gases to be compressed. The gas particles act independently of one another. Kinetic energy (bounce into each other and
the walls of the container) depends on the mass and velocity of an object. A body possesses kinetic energy when it moves. The kinetic energy of
the gas particles is directly proportional to the absolute temperature of the gas (e temp e velocity). Reporting the volume of the gas alone is
never enough (include the volume that your gas sample would occupy at standard temperature and pressure STP). Atmospheric pressure is the
force exerted by the atmosphere on the Earths surface. At the top of Mt. Everest, the atmospheric pressure is only one-fourth of that at sea level.
Pressure increases underwater because the water pressure adds to the atmospheric pressure. Physical properties of a gas depend on P (atm) / V
(Litres)/ T (Kelvin) / n (mole). Physical properties of all gases are similar (chemical properties vary). Units of measurement: 1 atm = 760
mmHg = 760 Torr (mmHg & Torr are the same). STP is O Celcius and 1 atmosphere of pressure.

Boyles Law = Pressure and volume of a gas at constant temperature are inversely proportional. If you e the volume of a gas, without changing
the temperature or number of particles, pressure will e. Above: The volume has decreased & the inside surface area has also decreased. This
means that the frequency of collisions per unit area has increased, which translates into an increase in pressure. e volume (compress the gas)
density (mass remains the same) and pressure will e. PV = Constant
Charles Law = As temp es, volume es. Temperature (heat) provides energy to a sample. When atoms are energized (heated), they move
around a lot and hit the sides of their containers harder and more often causing it to expand. An increase in temperature causes the pressure
within the syringe to increase, pushing out on the plunger. V/T = Constant
Gay-Lussacs Law = As temperature es, pressure es. If the temperature of the air in the syringe increases while keeping the volume constant,
the gas particles speeden up and make more frequent and stronger collisions with the inside walls of the syringe barrel leading to increased
pressure. Volume and no. of gas particles will not change. P/T = Constant
Combined Gas Law = Made up of the general rules for temperature, volume, and pressure described in Boyles, Charles, and Gay-Lussacs laws.
Volume of gas is directly proportional to the absolute temperature and inversely proportional to the pressure. PV/T = constant
Avogadros Law = Volume of a gas number of molecules present. If temperature and pressure are held constant and somehow more molecules
are added to the syringe, the volume will increase. V/n = Constant. Avogadros hypothesis: Equal numbers of molecules of any gas will occupy
the same volume and will exert the same pressure (at a particular temperature). One mole of any gas (6.02 1023 molecules) occupies a volume
of 22.4L and will exert a pressure of 760 mmHg (at 0C).
Gas Law

Boyle
Charles
Gay-Lussac
Avogadro

Variable
Pressure & Volume
Volume & Temperature
Temperature & Pressure
Volume & Moles

Relationship
Inverse
Direct
Direct
Direct

Ideal (General) Gas Law The ideal gas law relates the four quantities pressure, volume, moles (number of particles), and temperature. R is
called the ideal gas law constant. n = no. of moles of the gas. PV = nRT.
Daltons Law of Partial Pressures states that in a mixture of gases each gas exerts a pressure independent of the pressure exerted by other
gases in the mixture. The pressure of the individual gases in the mixture is the partial pressure of that gas. The sum of the partial pressures is
the total pressure. Partial pressure is directly related to the moles (concentration / content) of that gas present in the mixture. The partial
pressures of gases in our atmosphere are approximately 0.78 atm for N2, 0.21 atm for O2, and 0.01 atm for all the other gases combined.
Important = The pressure contribution of a particular gas (partial pressure) depends on the relative no. of molecules of that gas in the
mixture. Twice as many molecules will e the pressure 2 fold.
Henrys Law = The volume of a gas absorbed by a liquid with which it does not combine chemically is directly proportional to the pressure of
the gas to which the liquid is exposed & its solubility in the liquid.
Grahams Law = Under equal conditions of temperature and pressure, gases diffuse at a rate that is inversely proportional to the square roots of
their molecular masses.
1 mmHg = 1.36 cmH2O
Diving: Another area in which the gas laws play a key role is in scuba diving. At the surface, we breath air at a pressure of approximately 1
atmosphere. The partial pressures of N2 & O2 are 0.78 and 0.20 atmosphere, respectively. A scuba diver takes in compressed air that is delivered
at a pressure that corresponds to the pressure at the depth of the diver. Because 33 feet of water corresponds to 1 atmosphere of pressure, a
diver at 33 feet would breath air at a total pressure of 2 atmospheres (760 2 mmHg); one atmosphere of this pressure is due to the air pressure
at sea level and 1 atmosphere is due to the pressure of the water. The partial pressures of the N 2 & O2 would be twice as great as that at the
surface.

Concept: If a gaseous mixture of O2, N2, CO2 & H2O (typical mixture found in alveolar gas) was enclosed in a sealed container, it would develop a
pressure on the walls of the container, by the mechanism of collision between the gas molecules and the container walls. The force or pressure
developed by all the molecules of the mixture as they bounce off the container walls is the total pressure exerted by the gas. The partial pressure of any
component is the pressure developed by the molecules of that component acting alone. We could measure the partial pressure of any component by
removing the other components and determining the remaining pressure. In a mixture of gases, the partial pressure of a given gas is directly
proportional to the volume that gas contributes to the total volume. Fraction (21% for O2) of any gas is the ratio of the volume of that gas to the total
volume of all gases. The lungs and airways are always moist, and inspired gas is rapidly saturated with water vapor in the upper segments of the
respiratory system. The temperature in the airways and lungs is almost identical with deep body temperature (37C) & at this temperature water vapor
has a partial pressure of 47 mmHg (gaseous form of a liquid is termed a vapor).
SYMBOLS IN PULMONOLOGY

= denotes average

= given quantity per unit time

V = Volume of Gas (ml)

L = Lung

Q = Volume of Blood (ml)

F = Fractional Concentration (%)

V = Volume of Gas per unit time (or) Gas Flow (ml/min)

S = Saturation of Hb with O2

V E = Minute Ventilation

P = Pressure (or) Partial Pressure of a Gas

Q = Volume of blood per unit time (or) Blood Flow (ml/min)

C = Content (or) Concentration of gas in blood (ml/dl)
V CO2 = CO2 production

= denotes end capillary

E = Mixed Expired
T = Tidal

D = Dead Space

v = Mixed Venous

I = Inspired

c = End Capillary

Respiratory Rate = 12/min

V A = Alveolar Ventilation
VD = Dead Space Volume

V O2 = O2 consumption
VT = Tidal Volume

R = Respiratory Exchange Ratio

B = Barometric

The volume of a number (n) of gas molecules depends on the temperature (T) and the ambient pressure (P). Since pressure and temperature
affect the volume of a gas, care must be taken in describing volume (ambient temperature means surrounding temperature).

V=

nRT
P

Conventions used to describe a volume of Gas:

BTPS = Body Temperature & Pressure, Saturated [exhaled air. pulmonary volumes and flows are reported using this convention]

ATPS = Ambient Temperature & Pressure, Saturated [expired air, as found in a spirometer that has cooled down to room (ambient)
temperature but is still saturated with water vapor]

STPD = Standard Temperature & Pressure, Dry [standard temperature is 273.2 Kelvin (or) 0 C. standard pressure is 760 mmHg (or) 1
atm. convention used to report O 2 & CO2 dissolved in blood and body tissues]

ATP = Ambient Temperature & Pressure [room air]

One mole of any gas (6.02 1023 molecules) occupies a volume of 22.4L and will exert a pressure of 760 mmHg (at 0C). 273 = factor to convert
C to Kelvin. Pressure is defined as force (weight) per unit area (P=F/A). The density of a substance is its mass per unit volume.
Density = mass / volume. P = hdg (Pressure = height of column density gravitational acceleration). Total pressure at any point in a liquid =
atmospheric pressure + hdg. Pascals Law states that pressure exerted at a point in an enclosed and non-compressible liquid is transmitted
equally & undiminished in all directions. The air or the atmosphere around the earth extends upwards up to about 300 km from the sea level. The
density of air is maximum at sea level and becomes rarer as we go higher up (due to gravitational pull of the earth, air is more dense close to the
surface of the earth). Atmospheric pressure decreases as we go to higher and higher altitudes, since the density of air also decreases.
Partial Pressure of a Gas in a Liquid: Gases such as CO2, O2 and N2 that are in physical solution in a liquid such as plasma, continually escape
from the liquid into the gas phase and may also return to the liquid. When the rate of a gas coming out of solution is equal to the rate at which it
enters the solution, the system is in equilibrium for that gas and liquid. At equilibrium, the partial pressure of a gas in gas phase is equal to the
partial pressure of the gas in liquid phase.

PROBLEMS
Comatose patient with no spontaneous respiration is on mechanical ventilation & few measurements are made. The first 3 are ventilator settings.
U = Unknown Value
VT = 1L

RR = 10/min

FIO2 = 0.40 (40%)

PaCO2 = 40 mmHg

PECO2 = 30 mmHg

PaO2 = 95 mmHg

Minute Ventilation (V E) = VT RR = 10 L/min

Dead Space to Tidal Volume Ratio (VD/VT) = (40 mmHg 30 mmHg)/40 mmHg = 0.25 (dead space is 25% of the tidal volume)
Dead Space Volume (VD) = 250 ml
Alveolar Volume (VA) = VT VD = 750 ml
Alveolar Ventilation (V A) = VA RR = 7.5 L/min
If extra tubing with a volume of 250 ml were added to the system the new VD = 500 ml; new VA = 500 ml & the new VD/VT = 0.50
New PaCO2. V CO2 = PaCO2 V A. Assuming V CO2 to be constant & substituting we get : 40 7.5 = U 5. U = 60 (new PaCO2 = 60 mmHg)
Without extra tubing the ventilator settings are changed. VT = 500 ml; RR = 20/min. Dead space is the same (250 ml)
V E = 10 L/min; VA = 500 250 = 250 ml; V A = 250 20 = 5 L/min; VD = 250 ml; VD/VT = 250/500 = 0.50
New PaCO2. 40 7.5 = U 5; U = 60 (new PaCO2 = 60 mmHg)
New PECO2. VD/VT = (PaCO2 - PECO2)/PaCO2; 0.50 = (60 U)/60; U = 30 mmHg; PECO2 = 30 mmHg
In both above cases the proprtion of dead space ventilation is larger thereby decreasing alveolar ventilation & leading to hypercapnia.
Using all original values
PAO2 = FIO2 (PB 47) PACO2/R = 0.40 (713) 40/0.8 = 285 50 = 235 mmHg
AaDO2 = 235 95 = 140 mmHg
Patient improves and the following values apply when breathing room air. Now PaO2 = 75 mmHg & PaCO2 = 40 mmHg. Now AaDO2 = 100
75 = 25 mmHg. The next day the values while breathing room air are PaO2 = 80 mmHg & PaCO2 = 20 mmHg. Now AaDO2 = 125 80 = 45
mmHg
Problems are from P369 (Principles of Pulmonary Medicine). Below information also taken from Principles of Pulmonary Medicine.

Terminal bronchioles are the smallest units that do not actually participate in gas exchange.
The acinus includes structures distal to a terminal bronchiole: respiratory bronchioles, alveolar ducts, and alveoli (alveolar sacs).
The relationship between transpulmonary pressure and lung volume is the compliance curve of the lung.
At FRC the tendency of the lung to become smaller (inward elastic recoil of the lung) is exactly balanced by the tendency of the chest wall to
expand (the outward elastic recoil of the chest wall). These 2 factors + dynamic hyperinflation (see below) are the determinants of FRC.
At TLC (high lung volumes) it is primarily the stiffness of the lungs that prevents even further e in volume by inspiratory muscle action. Therefore
the primary determinants of TLC are the expanding action of the inspiratory musculature balanced by the inward elastic recoil of the lung.
At RV (low lung volumes) it is primarily the stiffness of the chest wall that prevents even further e in volume by expiratory muscle action. Therefore
the primary determinants of RV are the contracting action of the expiratory musculature balanced by the outward chest wall recoil force. With age or
with disease of the airways RV also depends on the tendency for airways to prematurely close during expiration and for gas trapping to occur called
dynamic compression.
Wasted ventilation is called dead space & wasted perfusion is called shunt.
ed V/Q = think dead space (when you die you go to heaven, implied by the up arrow). ed V/Q = think shunt (cunt goes to hell)
When a normal individual exercises V CO2 increases, but V A increases proportionately so PaCO2 remains constant.
Fraction of the tidal volume represented by the dead space, VD/VT = (PaCO2 - PECO2)/PaCO2 [Bohr Equation]
Each tidal volume (V T) breath can be divided into alveolar volume (VA) and dead space volume (VD), just as the total minute ventilation (V E) can be
divided into alveolar ventilation (V A) and wasted (or) dead space ventilation (V D).
PaCO2 is inversely proportional to alveolar ventilation and not to minute ventilation.
Because of O2 uptake and CO2 excretion at the alveolar-capillary interface, PAO2 is less than the 150 mmHg that was calculated for inspired gas
within the airways.
3 main factors determine tissue O2 delivery = PaO2 + Hb level + CO. The first 2 factors will determine CaO2.
The quantity of O2 consumed at the tissue level is the difference between the arterial and venous O 2 contents = 20 15 = 5 ml O2/100 ml blood =
50 ml O2/1L blood.
Total O2 consumption (V O2) = CO (CaO2 - CvO2) = 5 L/min 50 ml O2/L = 250 ml O2/min
The oxygenation status of Hb is important in determining the quantity of CO 2 that can be bound to Hb (deoxyHb having a greater affinity for CO 2
than oxyHb, known as the haldane effect). Oxygenation of Hb in the pulmonary capillaries decreases its ability to bind CO 2 and facilitates the
elimination of CO 2 by the lungs.
A disturbance in the relationship between ventilation and perfusion even if the total amounts of ventilation and blood flow are normal, is
frequently responsible for abnormal gas exchange in disease states.
If blood having a higher PCO2 and CO2 content mixes with an equal volume of blood having a lower PCO2 and CO2 content, an intermediate PCO2 and
CO2 content (approximately halfway between) results. In marked contrast, blood with a higher than normal P O2 does not have a correspondingly
higher O2 content and cannot compensate for blood with a low P O2 and low O2 content. The difference stems from the shape of the ODC.
AaDO2 is because of 2 factors. Small amount of CO behaves as a shunt without ever going through the pulmonary capillary bed (and) V/Q ratios
from the top to the bottom of the lung result in somewhat less-oxygenated blood from the bases combining with better-oxygenated blood from the
apices. AaDO2 normally is less than 15 mmHg, but it increases with age.
Shunt Causes: Intra-cardiac RL / pulmonary AVM / filling of the alveolar spaces with fluid / complete alveolar collapse.
Ventilation-perfusion mismatch and shunting are the two important mechanisms for elevation of the alveolar-arterial O2 difference. Diffusion block
rd
is a 3 not so important cause. A specialized circumstance in which a diffusion block plus more rapid transit of erythrocytes together contribute to
hypoxemia occurs during exercise in a patient with interstitial lung disease. In the nonexercising patient, a diffusion block should be considered only
a hypothetical rather than a real mechanism for increasing AaD O2 and causing hypoxemia.
Hypoventilation is relatively common in lung disease and can easily be identified by the presence of a high PCO2 accompanying the hypoxemia.
Decreasing the tidal volume and increasing the frequency of breathing you are increasing the relative proportion of dead space to alveolar
ventilation with the total minute ventilation being constant.
Hypercapnia Causes: e in minute ventilation, e in the proportion of wasted ventilation (ed dead space), and significant ventilation-perfusion
mismatch. Death makes you think of CO2 = Dead Space therefore es the PaCO2. By increasing the total minute ventilation, a patient often is
capable of compensating for the latter two situations so that CO 2 retention does not result.

FEF25%-75% is a relatively sensitive index of airflow obstruction and may be abnormal when the FEV 1/FVC ratio is still preserved. FEV1/FVC is the
most important number used to determine the presence of airflow obstruction.
The diffusing capacity is a measurement of the rate of transfer of gas from the alveolus to Hb within a capillary, measured in relation to the driving
pressure of the gas across the alveolar-capillary membrane. Small concentrations of CO are used for this purpose. Correct for Hb concentration.
Regarding PFTs consider an observed value to be abnormal if it is < 80% of the predicted value. Normal FEV 1/FVC ratio is 0.70 (es with age).
An obstructive pattern (asthma, chronic bronchitis, and emphysema) consists of a decrease in expiratory airflow rates (decrease in FEF 25%-75% and
FEV1/FVC ratio). High RV and RV/TLC ratio indicates air trapping owing to closure of airways during forced expiration. Increased TLC
(hyperinflation) is often found particularly in patients with asthma or emphysema. Diffusing capacity tends to be decreased in patients who have
loss of alveolar-capillary bed (as seen in emphysema) but not in those with chronic bronchitis and asthma.
The hallmark of restrictive disease is a reduction in lung volumes, whereas expiratory airflow rates are normal. A wide variety of parenchymal &
extra-parenchymal (pleural / neuromuscular / chest wall abnormalities) diseases show a restrictive pattern. The finding of a relatively high RV can
indicate either expiratory muscle weakness or a chest wall abnormality that makes the thoracic cage stiff (non-compliant) at low volumes.
Tests that detect early obstruction to airflow in the small or peripheral airways = maximal expiratory flow-volume loops / analysis of closing
volume / and FEF25%-75%. In patients with early airflow obstruction (perhaps localized to small airways), the contour of the terminal part of the
expiratory curve may be abnormal even when the FEV1/FVC ratio is normal.
A test of airflow that is commonly used in asthmatics is the Peak Expiratory Flow Rate. The patient blows out from TLC as hard as possible into a
simple readily available device that records the maximal (or peak) expiratory flow rate. Patients with asthma frequently record serial PEFR
measurements at home as a way of self-monitoring their disease.
ABG: 3 measurements are routinely obtained: PaO2 / PaCO2 / pH. AaD O2 can be calculated.
The O2 content of the blood does not begin to fall significantly until the PaO2 drops below 60 mm Hg.
PaO2 normally is between 80 and 100 mmHg, but the expected value depends significantly on the patients age and the level of P CO2 (reflecting
alveolar ventilation - an important determinant of alveolar & secondarily arterial P O2).
+
When PCO2 rises acutely, carbonic acid is formed and the concentration of H also rises (pH therefore falls).
Pulse Oximetry: Oxygenated and deoxygenated Hb have different patterns of light absorption, and measurement of the pulsatile absorption of light
by arteriolar blood passing through the finger allows quantitation of the two forms of Hb. Limitations: Results are inaccurate in the presence of an
abnormal Hb such as COHb / measures O2 saturation rather than PO2 / no information is provided about CO2 elimination and acid-base status.
Exercise Testing: Treadmill or a stationary bicycle. Measurements that can be made include work rate, HR, ventilation, O 2 consumption, CO2
production, expired gas tensions, & ABGs.
Scattered between the ciliated epithelial cells are goblet cells (mucosa) which produce mucus. However, the largest portion of mucus is made by
the bronchial mucous glands (submucosa). At the level of the terminal bronchioles and below the goblet cells are replaced by clara cells. With
chronic irritation the mucous glands hypertrophy; the goblet cells become more numerous and are found more distally than usual.
The elastic recoil pressure (not the pleural pressure produced by a maximal expiratory effort) is the important determinant of maximal expiratory
flow at least in the effort-independent or latter part of a forced expiration. The equal pressure point moves peripherally (toward smaller airways) as
lung volume decreases during a forced expiration.

Pathophysiology of asthma: Contraction of smooth muscle in the bronchial walls, mucosal edema, and secretions within the airway lumen all contribute to a
decreased airway diameter, which increases airway resistance. During expiration, relatively positive intrapleural pressure is transmitted to the airways, thus
decreasing their diameter. Therefore, greater difficulty with airflow on expiration than on inspiration is characteristic of asthma (as it is of any of the diseases
that cause narrowing of airways within the thorax). The greatest difficulty with expiration occurs when the patient is asked to perform a forced expiration.
PFTs during an attack show decreases in forced expiratory flow rates as well as evidence of air trapping. Measurement of lung volumes shows evidence
of air trapping, with increases in FRC, RV and TLC. Of all these lung volumes, the most impressive increase is seen in RV (due to premature airway closure).
FRC es because of dynamic hyperinflation (when airways are obstructed, patients may not have sufficient time to fully exhale the volume from the
previous breath before the next breath. This is especially a problem when the RR is high). TLC is ed because of ed inspiratory muscle strength. Decreased
FEV1, FVC, FEV1/FVC ratio & FEF25%-75%. Even between attacks, subtle abnormalities in pulmonary function are usually present, such as a decrease in
FEF25%-75% and a mild increase in RV (reflects residual disease in the small airways of the lung). With long-standing disease a component of irreversibility is
added to the picture. The most common pattern of ABGs in asthma is a low PaO2 (attributable primarily to V/Q mismatch) and a low PaCO2 (respiratory
alkalosis). The increased airway resistance in asthma is not evenly distributed, such that some airways are affected more than others. Inspired air tends to go
to less diseased areas. However, blood flow remains relatively preserved in the regions that are ventilating poorly. Activation of irritant receptors stimulate
ventilation PCO2 usually is low. PaCO2 that is normal or elevated often means worsening airflow obstruction or a tiring individual who is no longer able to
maintain ventilation in the face of significant airflow obstruction (serious warning sign).

Pathophysiology of COPD: Chronic bronchitis is a clinical diagnosis used for patients with chronic cough and sputum production. Unlike patients with
asthma they usually have residual clinical disease even between exacerbations (precipitated by respiratory tract infections), and their disease is not primarily
one of airway hyperreactivity. Emphysema is formally a pathologic diagnosis (destruction of alveolar walls and enlargement of terminal air spaces; region of
the lung from the respiratory bronchioles down to the alveoli is involved). Chronic bronchitis and emphysema coexist to a variable extent in different patients
(the broader term COPD is more accurate). Single etiologic factor cigarette smoking (on the airways CB; on the parenchyma E). The airway wall
becomes thickened because of the hypertrophied and hyperplastic mucous glands. Thickening of the wall diminishes the size of the airway lumen, and mucus
within the lumen further compromises its patency. At the same time that more mucus is produced in the larger airways, clearance of the mucus is altered by
effects of cigarette smoke on the cilia (impaired mucociliary clearance). Changes in the small airways or bronchioles are believed to be responsible for the
airflow obstruction in patients with COPD. Balance between neutrophil elastase and its inhibitor (1-antitrypsin) prevents destruction of alveolar septa.
Either an increase in neutrophil elastase activity or a decrease in 1-antitrypsin activity damages elastin and the alveolar walls, eventually producing
emphysema. Neutrophil elastase also stimulates mucus secretion. Matrix metalloproteinases are produced by macrophages and neutrophils and are
capable of breaking down components of the alveolar wall. Matrix metalloproteinases have a number of natural inhibitors called tissue inhibitors of matrix
metalloproteinases. Smoking Influx of neutrophils and macrophages Increased burden of matrix metalloproteinases capacity of the inhibitors

overwhelmed breakdown of alveolar walls. Occupational exposure to pollutants is an important factor contributing to COPD. Air pollution causes
exacerbations of preexisting disease. Infections cause transient worsening of symptoms and pulmonary function. Pathologic changes in the small airways
(bronchioles) are thought to be the primary cause of airflow obstruction in patients with COPD. Inflammation, fibrosis, intraluminal mucus, and an increase in
goblet cells decrease in luminal diameter. Panacinar emphysema = relatively uniform involvement of the acinus = 1-antitrypsin deficiency. Centriacinar
emphysema = predominant involvement and dilation are found in the proximal part of the acinus namely the respiratory bronchiole = smokers. Cigarette
smoking affects the large airways, the small airways, and the pulmonary parenchyma (disease at each of these levels contribute to the overall clinical picture
of COPD).
Chronic Bronchitis: In the larger airways (bronchi), an increase in the mucus-secreting apparatus and the amount of mucus produced results in the
symptoms of excessive cough and sputum production characteristic of chronic bronchitis (but this does not lead to obstruction). CB by involving the small
airways can produce only mild airflow obstruction. But when emphysema coexists the airflow obstruction is marked. Reason for airflow obstruction (ed
expiratory flow rates) in CB = small airway disease + emphysema. Airways resistance is increased by anything that compromises the lumen (intraluminal
secretions; bronchospasm; or thickening of the wall caused by edema, inflammatory cells, fibrosis, or enlargement of the mucus-secreting apparatus).
Decreased FEV1, FVC, FEV1/FVC ratio & FEF25%-75%. Use of inhaled bronchodilators may or may not result in improved flow rates (patients with asthmatic
bronchitis and greater airway reactivity have the most response). In patients with pure airway disease, TLC theoretically remains relatively close to normal
because neither the elastic recoil of the lung nor inspiratory muscle strength is altered. Similarly, FRC should remain normal because the recoil of the lung
and the recoil of the chest wall are unchanged. However, if expiration is prolonged and the RR is high then the patient will not have sufficient time during
expiration to reach the normal resting end-expiratory point dynamic hyperinflation ed FRC (Insufficient expiratory time in the face of significant airflow
obstruction). RV is also increased with processes that involve airways because the narrowing of small airways result in air trapping during expiration.
Emphysema: The primary problem in emphysema is loss of elastic lung recoil. One consequence of decreased elastic recoil is a decreased driving
pressure that expels air from the alveoli during expiration. In emphysema, decreased expiratory flow rates are due to loss of elastic lung recoil force resulting
in the following: [1] lower driving pressure for expiratory airflow; [2] Loss of radial traction on the airways (provided by alveolar septa). During a forced
expiration, the strongly positive pleural pressure promotes collapse. Airways lacking an adequate supporting structure are more likely to collapse and have
diminished flow rates and air trapping. The decrease in elastic recoil in emphysema also alters the compliance curve of the lung and the measured lung
volumes. Compliance curve is shifted upward and to the left (lung compliance is increased) and the lung has more volume at any particular transpulmonary
pressure. In pure chronic bronchitis without emphysema, the compliance curve is normal. TLC is increased because loss of elastic recoil results in a smaller
force opposing the action of the inspiratory musculature. FRC also is increased because the balance between the outward recoil of the chest wall and the
inward recoil of the lung is shifted in favor of the chest wall. As in bronchitis, RV is substantially increased in emphysema because poorly supported airways
are more susceptible to closure during a maximal expiration (air-trapping).
Gas Exchange in COPD: COPD guy is called a 50:50. Ventilation is not uniformly distributed throughout the lung (some airways are extensively affected by
secretions and plugging whereas others remain relatively uninvolved). This type of ventilation-perfusion disturbance, with some areas of lung having low
ventilation-perfusion ratios and contributing desaturated blood, leads to hypoxemia. Non-uniformity of the disease process results in V/Q mismatch and
hypoxemia. Mechanisms that contribute to alveolar hypoventilation and CO 2 retention (Hypercapnia) in COPD:
[1] Increased work of breathing (because of dynamic compression). ed airway resistance due to bronchial obstruction and narrowing of small airways results
in chronic hypoventilation. Also there is abnormality of central ventilatory drive
[2] V-Q mismatch creating some areas with high V-Q ratios (will act as dead space)
[3] Diaphragm is low / flat and its fibers are short even before inspiration begins (at a mechanical disadvantage compared with a longer curved diaphragm)
[4] Diaphragmatic fatigue (more important in pts. who are in respiratory failure)
Pulmonary Hypertension in COPD: The major cause of pulmonary hypertension in COPD is alveolar hypoxia. Additional less important factors include
acidosis / polycythemia (es viscosity of blood) & loss of the pulmonary vascular bed (destruction of alveoli is accompanied by a loss of pulmonary
capillaries). ed workload on the RV hypertrophy failure. Cor-pulmonale = disease of the RV secondary to any form of lung disease. If the hypoxia is
corrected, the element of pulmonary vasoconstriction may be reversible although in chronic hypoxia vascular remodeling occurs may not fully reverse.
2 Types of Presentation of COPD: Type A (pink puffer) & type B (Blue Bloater = Bronchitis). In most cases, a patient has some features suggestive of both.
Pink Puffer (Emphysema) = Gas-exchange abnormalities are not a striking feature

PaO2 tends to be well preserved (so that the patient is pink, that is the patient is not cyanotic). Relative preservation of Pa O2 may be related to a
simultaneous and matched loss of ventilation and perfusion when alveolar walls are destroyed.

Since significant hypoxia is absent there is no prominent stimulus for pulmonary hypertension

Elevated hematocrit (often a result of hypoxemia) not seen

Dyspnea and high minute ventilation are prominent features (puffing)

PaCO2 is not abnormally high

Blue Bloater (Chronic Bronchitis) = Major problems with gas exchange (hypoxemia and hypercapnia)

Cyanosis can result from significant hypoxemia (blue)

Patient is frequently obese and can have peripheral edema resulting from right ventricular failure (bloated)

Regions of lung supplied by diseased airways are underventilated while perfusion is relatively preserved in these same areas ( V/Q). The regions
of low V/Q contribute blood with a low PO2 (desaturated blood) that cannot be compensated for by increases in the V/Q ratio from other regions of
the lung arterial hypoxemia.

Hypercapnia (several mechanisms)

Pulmonary hypertension, cor-pulmonale, and elevated hematocrit values (secondary polycythemia) commonly accompany the clinical picture.
PFTs in COPD: [1] Airflow obstruction with decreases in FVC, FEV1, FEV1/FVC ratio, and FEF25%-75%
[2] Lung volumes generally give evidence of air trapping with an elevation in RV / FRC / TLC
[3] In patients with emphysema (surface area for gas exchange lost) the diffusing capacity is typically decreased. In pure airway disease (chronic bronchitis
without emphysema) the diffusing capacity is generally normal.

ABGs in COPD: Type A pts. have a normal or mildly decreased PaO2 and a normal or mildly decreased PaCO2. Type B pts have more strikingly abnormal
blood gas values (marked hypoxemia as well as hypercapnia). With chronic elevation in P CO2, the kidneys retain bicarbonate in an attempt to compensate and
return the pH towards normal. With acute exacerbations of COPD, hypoxemia frequently worsens and CO 2 retention becomes more pronounced.
Bronchiectasis: Irreversible dilation of airways caused by inflammatory destruction of airway walls. When an airway is obstructed, a superimposed infection
may develop behind the obstruction, causing destruction of the airway wall and leading to bronchiectasis. Tumors, thick mucus, or foreign bodies commonly
cause bronchial obstruction, resulting in bronchiectasis. Hypogammaglobulinemia / defective leukocyte function / dyskinetic cilia syndrome / ciliary
dysfunction all predispose. The dilated airways are generally filled with a considerable amount of grossly purulent secretions. History of copious sputum
production. Because of inflammatory changes in the bronchial wall, the blood supply provided by the bronchial arteries increases. Anastomoses form
between the bronchial and pulmonary artery circulations. Inflammatory erosion at the site of these vascular changes are responsible for the hemoptysis.
Cough becomes much less effective at clearing secretions because the weak damaged wall easily collapses. With localized disease PaO2 and PaCO2 are
normal. With diffuse disease patients may exhibit the blood gas changes seen in patients with the type B pattern of COPD (hypoxemia / hypercapnia / corpulmonale). Clubbing is thought to be associated with the chronic suppurative process.
Cystic Fibrosis: Thick mucous plugs in the bronchi obstruct airflow. As a result of airway obstruction, functional changes characteristic of obstructive airway
disease and air trapping (pneumothorax) develop. Resemble Type B COPD patients (V-Q mismatch / hypoxemia / pulmonary hypertension / cor-pulmonale /
hypercapnia in the later stages). PFTs: Generalized airway obstruction (decreased FEV1, FVC and FEV1/FVC ratio) & air trapping (increased RV/TLC
ratio) is seen. The elastic recoil of the lung is generally preserved, and TLC most commonly is within the normal range. Because emphysematous changes
are not usually seen in patients with cystic fibrosis and the alveolar-capillary interface remains relatively preserved the diffusing capacity is relatively normal.
Serious respiratory complications of CF include pneumothorax / massive hemoptysis / respiratory insufficiency / cor-pulmonale.
Upper Airway Disease: Disorders affecting the pharynx, larynx, and trachea (above main carina) producing upper airway obstruction. Bronchi &
bronchioles = lower airways. Acute obstruction usually happens at the level of the larynx. These include infection (epiglottitis, which often is due to
Haemophilus influenzae) / thermal injury and the resulting laryngeal edema from smoke inhalation / foreign body aspiration / laryngeal edema from an allergic
(anaphylactic) reaction / physical trauma associated with endotracheal intubation. Chronic obstruction = hypertrophy of the tonsils / tumors (particularly of the
trachea) / strictures of the trachea (from prior instrumentation) / vocal cord paralysis / recurrent episodes of upper airway obstruction during sleep in sleep
apnea syndrome. If the airways were stiff (disorder did not allow any flexibility in the size of the airway) then inspiration and expiration would be impaired by
the same amount, and the flow rate generated during inspiration would be essentially identical to the flow rate during expiration. This type of obstruction is
termed a fixed obstruction. If airway diameter changes during the respiratory cycle = variable obstruction. If the obstruction is intrathoracic, then changes in
pleural pressure during the respiratory cycle affect the size of the airway and therefore the magnitude of the obstruction. During a forced expiration the
positive pleural pressure causes airway narrowing, making the obstructing lesion more critical. During inspiration, the airways increase their diameter and the
effects of a partial obstruction are less pronounced. If the obstruction is extrathoracic, the negative airway pressure during inspiration tends to create a
vacuumlike effect on extrathoracic upper airways, narrowing them and augmenting the effect of any partial obstruction. During expiration the pressure
generated by the flow of air from the intrathoracic airways tends to widen the extrathoracic airways and to decrease the net effect of a partially obstructing
lesion. If the lesion is variable and intrathoracic, the primary difficulty with airflow occurs during expiration and patients demonstrate expiratory wheezing. If
the lesion is variable and extrathoracic obstruction is more marked during inspiration and patients frequently manifest inspiratory stridor best heard over the
trachea. PFTs: With a fixed obstruction a plateau marks both the inspiratory and expiratory parts of the flow-volume curve. When the lesion is variable, the
effect of the obstruction depends on whether the lesion is intrathoracic or extrathoracic. With an intrathoracic variable obstruction the expiratory part of the
flow-volume curve displays a plateau. With an extrathoracic variable obstruction the inspiratory portion displays the plateau.
Pulmonary Parenchyma: The trachea, bronchi, and bronchioles down to the level of the terminal bronchioles constitute the conducting airways (their
function is to transport gas). The pulmonary parenchyma includes: the alveolar walls and spaces (with the alveolarcapillary interface) at the level of the
alveolar sacs, ducts, and respiratory bronchioles (region of the lung directly involved in gas exchange). Respiratory bronchioles are considered part of the gas
exchanging region of lung because alveoli are present along their walls. With successive generations of respiratory bronchioles, more alveoli appear along
the walls up to the site of the alveolar ducts, which are entirely alveolarized. Disorders involving these structures = interstitial lung disease (or) diffuse
parenchymal lung disease. Type I cells are less numerous than type II cells. They have long cytoplasmic extensions that line more than 95% of the alveolar
surface. Type I cells function as a barrier. Type II cells have 2 well-defined functions: synthesis of surfactant & alveolar epithelial repair. In contrast to type I
cells, type II epithelial cells have a cuboidal shape and often bulge into the alveolar lumen. Because they do not have long cytoplasmic extensions, type II
cells cover less than 5% of the alveolar surface. Specifi c inclusion bodies within the type II cells, termed lamellar inclusions, appear to be the packaged form
of surfactant that eventually is released into the alveolar lumen. Surfactant acts like a detergent reducing the surface tension of the alveoli. Type I epithelial
cells are quite susceptible to a variety of injurious agents, whether the agents reach the alveolar wall via the airways or the bloodstream. When type I cells are
damaged, the reparative process involves hyperplasia of the type II cells and eventual differentiation into cells with the characteristics of type I cells. Unlike
the alveolar epithelial cells, which are quite impermeable, junctions between capillary endothelial cells permit passage of small-molecularweight proteins.
At some regions nothing stands between the epithelial and endothelial cells other than the basement membranes, which are fused to form a single structure.
At other regions, the interstitial space intervenes. Within the alveolar lumen a thin layer of liquid covers the alveolar epithelial cells. This alveolar lining
layer is composed of an aqueous phase immediately adjacent to the epithelial cells covered by a lipid-rich surfactant layer. The barrier to diffusion is
extremely thin, measuring approximately 0.5 m. Some areas of the alveolar wall also contain a thin layer of interstitium, but gas exchange occurs
preferentially at the thinnest region, where the interstitium is sparse or absent. Impaired diffusion across an abnormal alveolar-capillary interface is not a
primary contributor to the disturbance in gas exchange when the patient is at rest. However when a patient exercises and increases CO, blood flows more
rapidly through the pulmonary capillaries, and the combination of a diffusion impairment and less time for diffusion of oxygen may lead to hypoxemia. The
compliance curve of the lung in ILD is shifted downward and to the right (a lower volume is achieved for any given transpulmonary pressure).
Diffuse Parenchymal Lung Disease (DPLD) (or) Interstitial Lung Disease (ILD):
A large group of disorders that ultimately lead to to diffuse scarring or fibrosis of the alveolar wall. Interstitial lung diseases affect all components of the
alveolar wall: epithelial cells, endothelial cells, and cellular and noncellular components of the interstitium. The disease process often extends into the alveolar
spaces and therefore is not limited to the alveolar wall. ILD is therfore a misnomer. There are more than 150 diffuse parenchymal lung diseases (important
ones listed below). Primarily chronic (or) subacute diseases affecting the alveolar structures are included here. Acute injury to components of the alveolus
will be called ARDS (acute respiratory failure). Diffuse parenchymal lung diseases regardless of cause have two major pathologic components: an
inflammatory process (in the alveolar wall and alveolar spaces) sometimes called alveolitis (and) a scarring (fibrotic) process. Proportions of inflammation
and fibrosis vary cause & duration. Active inflammation is the primary process and fibrosis follows as a secondary feature (idiopathic pulmonary fibrosis is an
exception to this generalization). When DPLD has been present for a fairly long time and is associated with significant fibrosis, any distinctive features of a
particular type of DPLD is lost (any of the granulomatous lung diseases may no longer demonstrate the characteristic granulomas). After a certain point all
follow a final common pathway (end-stage DPLD) characterized by dense scarring and intervening cystic regions (honeycomb lung). Patients have a
restrictive pattern on PFT with decreased lung volumes and preserved airflow.
Pathophysiology of DPLD: Inflammation followed by fibrosis affecting the alveolar walls results in the following:
[1] ed Compliance: The lungs become much stiffer, have a greatly increased elastic recoil, and therefore require greater transpulmonary pressures to
achieve any given lung volume (WOB is increased). The compliance curve is shifted to the right. Tend to breathe with smaller tidal volumes but with
increased RR (to reduce the WOB).
[2] e in Lung Volumes: Decrease in TLC, FRC, VC and to a lesser extent RV (direct consequence of the ed inward elastic recoil of the lung). At TLC,
the force generated by the inspiratory muscles is balanced by the inward elastic recoil of the lung. Because the recoil pressure is increased, this balance is

achieved at a lower lung volume or lower TLC. At FRC, the outward recoil of the chest wall is balanced by the inward elastic recoil of the lung. The balance is
achieved at a lower lung volume or lower FRC because of the greater elastic recoil of the lung. RV is primarily determined by the strength of the expiratory
muscles (however, a small component is determined by the inward elastic recoil of the lungs). Because the elastic recoil is greater in diffuse parenchymal
lung disease, the RV is slightly smaller. TLC is reduced more than RV, therefore VC will e.

[3] ed DL: Although thickening of the alveolar-capillary interface (because of interstitial inflammation and fibrosis) might be expected to be responsible for this
decrease, it is not the major factor. Rather inflammation and fibrosis destroy a portion of the alveolar-capillary interface thus reducing the surface area
available for gas exchange.
[4] Abnormal Small Airways: Large airways generally function normally in these patients, and the FEV1/FVC ratio is normal or even increased. Inflammation
and fibrosis also affect the small airways (just an extension of the same process that occurs in the alveolar wall) with narrowing of the lumen of the
small airways or bronchioles. V/Q mismatching and hypoxemia are consequences. Rarely in some kinds of DPLD significant airflow obstruction may be seen
secondary to severe fibrosis causing airway distortion.
[5] Gas Exchange: Hypoxemia with normo (or) hypocapnia. V/Q mis-match (because of uneven pathologic process) is the major cause of hypoxemia (and
not diffusion block). Patients with interstitial lung disease become even more hypoxemic with exercise (diffusion-limited gas exchange because of impaired
diffusion and decreased transit time of the red blood cell during exercise). P CO2 is generally normal or low because patients are able to increase minute
ventilation sufficiently to compensate for a decrease in tidal volume and for any additional dead space. Elevation of P CO2 does not generally occur until the
very late stages of the disease.
[6] Pulmonary Hypertension: PH is common in severe ILD resulting from hypoxemia (and) obliteration of small pulmonary vessels by the fibrotic process.
During exercise pulmonary hypertension becomes even more marked due to the limited ability of the pulmonary capillary bed to distend and recruit new
vessels (to handle the exercise-induced increase in cardiac output). PH leads RV hypertrophy & cor-pulmonale.
Clinical Presentation of DPLD: Dyspnea (initially on exertion but with severe disease may be experienced even at rest) / Nonproductive cough / Crackles at
lung bases / Clubbing (with certain types of ILD). The characteristic radiographic picture is an interstitial pattern, described as either reticular (increased linear
markings) or reticulonodular (increased linear and small nodular markings). The interstitial pattern reflects a process involving the alveolar walls.

Pulmonary Vasculature: pulmonary arteries and their branches travel with companion airways, following closely the course of the progressively dividing
bronchial tree. With a means for increasing the total cross-sectional area of the pulmonary vasculature on demand (via recruitment & distension) the
pulmonary circulation is capable of lowering its resistance when the need for increased flow arises. Because the top of the lung is approximately 15 cm above
the level of the main pulmonary arteries, a pressure of 15 cm H 2O is required to achieve perfusion of the apices. The MPAP of 15 mmHg (approximately 19
cmH2O) normally is just sufficient to achieve flow to this region. At the lung bases (zone 4 = most dependent region of the lung) the weight of the lung
compresses the alveoli & the extra-alveolar vessels resulting in decreased alveolar volume and ed resistance of the extraalveolar vessels. The total vascular
resistance in this zone increases and blood flow diminishes. HPV serves to e V-Q mismatch (blood flow to areas with a low V-Q ratio, which contribute

hypoxemic blood, is minimized). A protective response in the case of localized disease but detrimental in the case of generalized disease and widespread
alveolar hypoxia (generalized HPV in response to alveolar hypoxia is beneficial only in one place: the fetus). HPV mechanism: alveolar hypoxia acting
directly (or) indirectly via NO (a potent vasodilator) & endothelin (a potent vasoconstrictor). An additional stimulus for pulmonary vasoconstriction is a low
blood pH value (acidosis). Hypoxia & low blood pH appear to have a synergistic effect on increasing PVR. Hypercapnia may increase PVR via changes in
blood pH. Serotonin and bradykinin are primarily inactivated in the lung.
Pulmonary Thromboembolism: Although these thrombi frequently originate in the veins of the calf, propagation of the clots to the veins of the thigh is
necessary to produce sufficiently large thromboemboli and become clinically significant. Major consequences of vascular occlusion in the lung parenchyma
distal to the site of occlusion:
[1] Pulmonary Infarction: Only 10% to 15% of all pulmonary emboli result in pulmonary infarction because compromise of 2 of the 3 O 2 sources to the lung
(pulmonary artery, bronchial artery, & alveolar gas) is necessary before infarction results. PI is followed by contraction of the infarcted parenchyma and
eventual formation of scar tissue.
[2] Congestive Atelectasis: When the integrity of the parenchyma is maintained and infarction does not result, parenchymal hemorrhage and edema occurs
in the lung tissue supplied by the occluded pulmonary artery. Resolution of the process and resorption of the blood may leave few or no pathologic sequelae.
With either pulmonary infarction or congestive atelectasis, the pathologic process may extend to the visceral pleural surface pleura based changes
(radiographic changes / pleural effusion / pleuritic chest pain / pleural friction rub).
[3] Neither of the above pathologic changes occur and there is relatively little alteration of the distal lung parenchyma presumably because of incomplete
occlusion (or) rapid clot dissolution.
Clots that do not fragment (with smaller fragments moving progressively distally in the pulmonary arterial circulation) or lyse slower process of organization
& eventual recanalization occurs.
Pathophysiology of Pulmonary Thromboembolism:
[1] Perfusion of pulmonary capillaries normally supplied by that vessel ceases. If ventilation to the corresponding alveoli continues, then the ventilation is
wasted, and the region of lung serves as dead space. Assuming that minute ventilation remains constant, increasing the dead space automatically
decreases alveolar ventilation and hence CO 2 excretion. However hypercapnia is an unusual consequence of pulmonary embolism because patients
routinely increase their minute ventilation after an embolus occurs and more than compensate for the increase in dead space. In fact, the usual consequence
of a pulmonary embolus is hyperventilation and hypocapnia. However, if minute ventilation is fixed (unconscious or anesthetized patient whose ventilation is
controlled by a mechanical ventilator), then hypercapnia may result from the increase in dead space.
[2] e in pulmonary vascular resistance: e in the size of the vascular bed by the combination of mechanical occlusion & the effects of chemical mediators
(chemical mediators released from the thrombus & ischemic tissue cause vasoconstriction). There is usually no increase in resistance or pressure in the
pulmonary vasculature until a large portion of the vascular bed is occluded (pulmonary vascular bed is capable of recruitment and distention). RV cannot
cope with the acute increase in workload and the forward output of the RV es may lead to forward (cardiogenic shock) & backward (raised JVP) failure.
[3] Thrombi release chemical mediators that have secondary effects on small airways (bronchoconstriction) and blood vessels (vasoconstriction) of
the lung (platelets in the thrombus are an important source histamine, serotonin, and prostaglandins). e in resistance in the small airways is an important
cause of hypoxemia.
[4] Synthesis of surfactant in the affected alveoli is ed alveoli are more likely to collapse & liquid leaks into alveolar spaces.
[5] Hypocapnic Bronchoconstriction of the small airways.
[6] Shunting also contributes to the hypoxemia (perfusion of atelectatic lung).
Acute onset of dyspnea is the most frequent complaint. ABG values show hypoxemia / respiratory alkalosis / hypocapnia / ed AaDO2. Occasionally PaO2 is
normal.
Pulmonary Hypertension: MPAP greater than 25 mmHg at rest or 30 mmHg with exercise (normal MPAP = 15 mmHg). May be acute or chronic,
depending on the causative factors. RV hypertrophy that occurs secondary to pulmonary hypertension caused by any intrinsic disorder of the respiratory
system is called cor-pulmonale. If the primary change is proximal (pulmonary arterioles) pulmonary capillary pressure is normal. If the primary change is
distal (pulmonary veins or left atrium) pulmonary capillary pressure is elevated. Causes are:
[1] e in cross-sectional area of the pulmonary vascular bed by material within their vessels such as pulmonary emboli. Massive pulmonary embolus RV
dilates. Chronic Thromboembolic Disease (CTD): multiple and recurrent small pulmonary emboli RV hypertrophy. In CTD there are no acute episodes & insitu thrombosis of the microvasculature (secondary to endothelial damage) may play a role.
[2] Primary thickening of arterial walls: Idiopathic Pulmonary Arterial Hypertension (IPAH; formerly called Primary Pulmonary Hypertension) is an example.
Usually severe with pressures ed at rest & with exercise.
[3] Total cross-sectional area of the pulmonary vascular bed is ed by parenchymal lung disease (loss of blood vessels because of fibotic process / scarring
affecting the alveolar walls). ILD & emphysema. Pressures are usually normal at rest & moderately elevate with exercise (because of insufficient recruitment
or distention).
[4] Vasoconstriction in response to alveolar hypoxia (or) less importantly acidosis. Potentially reversible when normal P O2 and pH value are achieved.
Acidosis (respiratory or metabolic) is less important than alveolar hypoxia (augments the vasoconstrictive response to hypoxia). Example is Type B COPD.
Goal is to maintain PaO2 > 60 mmHg (above this level HPV is largely eliminated).
[5] Increased pulmonary vascular flow like with congenital intracardiac left-to-right shunts. Over time, the vessel walls thickens and pulmonary arterial
resistance increases.
[6] ed pressures in the LA or LV transmitted backwards through the pulmonary veins & capillaries. The initial elevation in pressure is not accompanied by
anatomic changes (like above) in the pulmonary arteries, but over time medial hypertrophy sets in. Examples are MS & chronic LVF. The resulting RV
hypertrophy is not included in the category of cor-pulmonale (here pulmonary hypertension is clearly of cardiac origin). Long-standing pulmonary venous
hypertension is associated with extravasation of erythrocytes into the pulmonary parenchyma, hemosiderin-laden macrophages and a fibrotic interstitial
response. Fibrotic response is secondary to the long-standing extravasation of blood.
PH Pathology:
[1] Intimal hyperplasia and medial hypertrophy of small arteries and arterioles
[2] Eventual obliteration of the lumen of small arteries and arterioles thereby ing PVR
[3] Medial thickening of the wall of larger (elastic) pulmonary arteries
[4] High pressures endothelial damage In-situ thrombosis in the pulmonary vasculature worsening hypertension
[5] Concentric hypertrophy of the RV wall. With failure there is dilation
PFTs may demonstrate underlying airflow obstruction (from COPD) or restricted lung volumes (from ILD). As a result of the pulmonary hypertension itself and
loss of the pulmonary vascular bed the DL is decreased. ABGs to decide if hypoxia (or) acidosis plays any role in the pathogenesis. The most common
causes of cor pulmonale are COPD & ILD.
Pleura: Surface lining cells of the pleura are called mesothelial cells. Beneath the mesothelial cell layer is a thin layer of connective tissue through which
blood vessels and lymphatics course. The arterial supply and venous drainage of the parietal pleura is from the systemic circulation. The visceral pleura is
supplied by the bronchial circulation (part of the systemic circulation) but drains into the pulmonary venous system (because of this the hydrostatic pressure in
the visceral pleural capillaries is less than that in the parietal pleural capillaries therefore most of the small amount of normal pleural fluid comes from the
systemic capillaries of the parietal pleura. There is a net pressure favoring movement of fluid from the parietal pleura to the pleural space. Pleural fluid
(ultrafiltrate from the pleural capillaries) is formed from the parietal pleural surface, and absorbed through the stomata (openings between mesothelial cells
present only on the parietal pleural surface) into lymphatic channels of the parietal pleura. When using the starling equation the pericapillary interstial space is
essentially the pleural space. The intrapleural pressure (hydrostatic pressure within the pleural space) is negative.

Pleural Effusions: Transudative fluid usually implies that the pathologic process does not primarily involve the pleural surfaces, whereas exudative fluid
suggests that the pleura is affected by the disease process causing the effusion.
[1] Exudate: Increase in the permeability of the pleural surfaces so that protein and fluid more readily enter the pleural space. Inflammation or malignancy
involving the pleura. The inflammatory process may:

Originate within the lung and extend to the visceral pleural surface (infections like bacterial pneumonia & TB / pulmonary embolism)

Involve the pleura primarily (connective tissue diseases, particularly SLE & RA)

Inflammatory processes below the diaphragm (pancreatitis / subphrenic abscess). Inflammation of the diaphragm itself may lead to increased
permeability of vessels in the diaphragmatic pleura and leakage of fluid into the pleural space.
Malignancy may cause pleural effusion by several mechanisms, but the resulting fluid is usually exudative.

Commonly, malignant cells are found on the pleural surface, arriving there either by direct extension from an intrapulmonary malignancy or by
hematogenous (bloodstream) dissemination from a distant source.

Lymphatic channels or lymph nodes may be blocked by foci of tumor so that the normal lymphatic clearance mechanism for protein and fluid from
the pleural space is impaired (In this case malignant cells are not found on examination of the pleural fluid).
[2] Blockage of the lymphatic drainage from the pleural space when tumor cells invade the lymphatic channels or the draining lymph nodes. This is an
exudative effusion (protein & fluid not cleared).
[3] Transudate: Alteration of starling forces. Most frequently it is associated with CHF. The source of pleural fluid in CHF appears to be liquid leaking out of
the pulmonary capillaries lung interstitium across visceral pleura pleural space (traditionally the explanation has been: an elevation of hydrostatic
pressure in the pleural capillaries causing fluid flux into the pleural space). Pulmonary venous hypertension (from left-sided heart failure) leading to increased
hydrostatic pressure in the pulmonary capillaries appears to be a more important factor contributing to effusions than is systemic venous hypertension (from
right-sided failure) leading to increased hydrostatic pressure in the systemic (and therefore pleural) capillaries. Pleural effusion is most likely to occur when
both ventricles are failing. Decreased plasma oncotic pressure (nephrotic syndrome).
[4] Transudative Ascitic fluid travels to the pleural space via small diaphragmatic defects and by diaphragmatic lymphatics promoted by the ve intrapleural
pressure. Most important mechanism for the pleural effusions seen in cirrhosis. Hypoproteinemia (ed synthesis) has only a minor role.
PFTs: Not routinely done. A significant effusion will impair lung expansion and produce a restrictive pattern (with decreased lung volumes).
Pneumothorax: Once the defect is closed the air is spontaneously absorbed. Air within the pleural space has a pressure nearly equal to atmospheric
pressure (760 mmHg). In contrast gas pressures in mixed venous blood are approximately as follows: PO2 = 40 / PCO2 = 46 / PN2 = 573 / P H2O = 47. The total
gas pressure in mixed venous blood is 706 mm Hg (approx. 50 mmHg below that in the pleural space). There is a gradient for diffusion of gas from the pleural
space into mixed venous blood. As the size of the pneumothorax is reduced, gas pressures within the pleural space are maintained until all the air is
absorbed. With 100% O2 the above process will speeden up. In arterial blood, most of the N2 is replaced by O2. As a result P N2 in the capillary blood
surrounding the pneumothorax becomes quite low, and the gradient for absorption of N 2 from the pleural space has been increased (N2 is the main
component of gas in the pneumothorax). Although PaO2 is high after inhalation of pure O2, PO2 falls substantially in capillary and venous blood because of O 2
consumption by the tissues. Therefore a large partial pressure gradient from pleural gas to pleural capillary blood remains for O 2 as well.
Pneumomediastinum: 3 major sources:
[1] Through the chest wall (penetrating trauma)
[2] From a tear in the esophagus (or) trachea - allowing air to enter directly
[3] From the alveoli: ed intra-alveolar pressure air enters interstitial tissues of the alveolar wall dissects proximally along the brochovascular plane to
exit at the hilum mediastinum (Proximal dissection of extraalveolar air). MCC of pneumomediastinum. Severe coughing / vomiting / straining /
mechanical ventilation (positive pressures induce alveolar rupture and a pneumomediastinum). Pneumomediastinum in asthma is because of the
development of high intraalveolar pressure in a lung unit behind an obstructed bronchus (dynamic hyperinflation).
Pathophysiology of pneumomediastinum: When pressure builds up within the mediastinum, air dissects along fascial planes into the neck, allowing
release of the pressure thereby preventing disastrous cardiovascular complications (compression of major veins ing VR cardiogenic shock). With
continued entry of air into the soft tissues of the neck the air dissects through the soft tissues of the chest & abdominal wall (subcutaneous emphysema).
There may be rupture of the mediastinal pleura and air entry into the pleural space pneumothorax. Because of the escape route available for mediastinal
air major cardiovascular complications are uncommon. Subcutaneous emphysema, although unsightly & uncomfortable is not associated with major clinical
sequelae. In the rare circumstance when pressure builds up within the mediastinum placement of a catheter may be necessary to allow escape of air.

Respiratory Control System: One group of neurons is responsible for the degree of central inspiratory drive (which regulates the inspiratory flow rate) &
another group of neurons controls the timing mechanism (termination of inspiration and hence the onset of expiration). These two factors determine the tidal
volume and respiratory rate respectively. Increased blood PaCO2 Increased brain ECF PCO2 Decreased brain ECF pH Decreased pH at central
chemoreceptor Stimulation of central chemoreceptor Stimulation of medullary respiratory center Increased ventilation Decreased arterial blood
PCO2. The carotid chemoreceptors, are quantitatively more important than the aortic chemoreceptors. Arterial hypoxemia increases the sensitivity of the
peripheral PCO2 chemoreceptors. Input from Other Receptors: Stretch receptors (located within the smooth muscle of airway walls) / Irritant receptors (lining of
airways) / Juxtacapillary (or J) receptors (pulmonary interstitium adjacent to capillaries. J receptors are responsible for the tachypnea caused by inflammatory
processes or accumulation of fluid within the pulmonary interstitium). When PaO2 is held constant, ventilation es (linearly) as PaCO2 es. At a lower PaO2, the
response to hypercapnia is heightened. With chronic hypercapnia the ventilatory response to further increases in PaCO2 is diminished. When CO2 retention
persists for days, the kidneys compensate for the more acidic pH by excreting less bicarbonate, and the levels of bicarbonate rise in both plasma and brain
ECF. The elevated bicarbonate level can buffer more successfully any acute pH changes in brain ECF. With hypoxemia, the same linear relationship does
not exist (here it is curvilinear) between alterations in partial pressure and ventilation (the ventilatory response is relatively small until Pa O2 falls to
approximately 60 mmHg). The sensitivity to hypoxemia is increased as PaCO2 is raised and is decreased as PaCO2 is lowered. The peripheral chemoreceptors
appear to be primarily responsible for sensing acute metabolic acidosis and stimulating the increase in ventilation.
Diaphragm: At its lateral aspect, the diaphragm is adjacent to the inner part of the lower rib cage. This portion of the chest wall and the diaphragm is known
as the zone of apposition. In this region the muscle fibers of the diaphragm are oriented vertically. Diaphragm contracts shortening of the vertically oriented
fibers central dome of the diaphragm descends pushes abdominal contents downward increasing intra-abdominal pressure lateral pressure on the
lower rib cage also es lower chest wall expands (and at the same time the abdominal wall moves outward). With normal resting breathing, the most
apparent inspiratory motion is the outward movement of the abdomen, which results from diaphragmatic descent and increased abdominal pressure. The
effectiveness of diaphragmatic contraction is decreased at high resting lung volumes, when the diaphragm is lower, flatter and shorter. For any muscle, the
strength of contraction is decreased when its initial length is less. The low flat diaphragm means that the zone of apposition is decreased, with less downward
movement of the diaphragm and outward movement of the lower chest wall possible with effort. At the extreme, the diaphragm is oriented horizontally, there
is no zone of apposition, and contraction results in an indrawing of the lower rib cage (no useful inspiratory function). COPD = Resting lung volume is
abnormally high & even before the diaphragm begins to contract it is low, flat & short.
Disorders of Ventilatory Control: May be due to a primary disorder of the neurologic network involved in ventilatory control (or) may be secondary to
primary lung disease. Primary disorders may result in hyperventilation, hypoventilation (or) a change in the pattern of breathing.
[1] Hyperventilation: is common with several acute disorders of the central nervous system (meningitis / encephalitis / stroke / trauma / hyperthyroidism /
hepatic disease). Increased sensitivity of the chemoreceptors in the brain with hyperthyroidism. In hepatic disease there is increased blood levels of
substances (progesterone / ammonia / glutamate) stimulating ventilation that normally are metabolized by the healthy liver. Exact mechanism for others
uncertain.
[2] Hypoventilation: Characterized by depressed ventilatory responses to hypercapnia or hypoxia. Primary insult to the centers involved with control of
breathing / primary alveolar hypoventilation (idiopathic) / sequela of the past CNS insult like encephalitis / congenital central hypoventilation syndrome
(Ondines curse). Cor-pulmonale results. Can be treated with Progesterone (well known to be a respiratory stimulant) / repetitive electrical stimulation of the
phrenic nerve (inducing diaphragmatic contraction) / noninvasive positive-pressure ventilation (most common current therapy).
[3] Abnormal Patterns of Breathing: ataxic breathing / apneustic breathing / cheyne-stokes breathing.
Cheyne-Stokes Breathing: Common causes of are CHF / some forms of CNS disease / sleep onset / high altitude. Cyclic pattern in which periods of
gradually increasing ventilation (depth & frequency) alternate with periods of gradually decreasing ventilation even to the point of apnea. Problem with the
feedback system of ventilatory control. In CHF there is delayed response to the signal (prolongation in circulation time results in an abnormal delay between
events in the lung and sensing of PCO2 changes by the central chemoreceptor). In CNS disease there is an heightened responsiveness of the feedback
system resulting in cyclical overshooting and undershooting of ventilation. Cheyne-Stokes breathing is clinically common.

Secondary Disorders: Patients with asthma hyperventilation during acute attacks as a consequence of stimulation of airway irritant receptors. Type B COPD
pts. have hypercapnia & chronic compensated respiratory acidosis (higher levels of plasma as well as CSF bicarbonate because of bicarbonate retention by
the kidneys). For any increment in P CO2, the effect on pH at the medullary chemoreceptor is attenuated by the increased buffering capacity available (chronic
respiratory acidosis with a compensatory metabolic alkalosis blunts the responsiveness of the central chemoreceptor).Therefore the ventilatory response to
ing PCO2 in chronically hypercapnic patients (irrespective of the cause) is ed. Administration of O2 to the chronically hypoxemic & hypercapnic patient
(irrespective of the cause) may elevate PaCO2 even further (very high levels of inspired O2 lifethreatening CO2 retention). Two factors account for this
well-recognized clinical event:
[1] Withdrawal of Hypoxic Drive: Supplemental O2 pt. is no longer hypoxemic hypoxic drive on the peripheral chemoreceptors abates ed alveolar
ventilation CO2 retension (these pts are highly dependent on hypoxic drive as a ventilatory stimulus because there is loss of sensitivity to CO 2 as a
ventilatory stimulus secondary to the chronic compensated respiratory acidosis).
[2] V-Q Mismatching: Supplemental O2 ed alveolar hypoxia HPV deactivated V-Q mismatching es (note that HPV functions to match V & Q) less
efficient elimination of CO2 ed PaCO2 levels.
Do not withhold supplemental O2 from hypoxemic patients who have chronic hypercapnia because significant hypoxemia poses more of a risk than does a
further increase in PaCO2. Such patients are given limited amounts of supplemental O 2 (enough to just raise SaO2 to approximately 90%) in order to minimize
further hypercapnia.
Sleep Apnea Syndrome: Repetitive periods of apnea (period of more than 10 seconds without airflow) and hypopnea (reduction in airflow of 50% or more)
occur during sleep. Types = obstructive / central / mixed. With obstructive - Inspiratory muscles are active but their attempts at initiating airflow are futile.
Obstructive Sleep Apnea Hypopnea Syndrome:
[1] During Sleep: Snoring / agitation / violent movements / early morning headache because of cerebral vasodilation / deeper phases of sleep are not
achieved because of repeated microarousals. Short fat necks / micrognathia / large tongue / enlarged tonsils / obesity are all risk factors.
[2] Daytime Symptoms: daytime somnolence / cannot concentrate / depression
[3] Cardiovascular Complications: cardiac arrhythmias or conduction disturbances / pulmonary hypertension / systemic hypertension / cor-pulmonale.
Inspiration involves not only contraction of the diaphragm (resulting in negative airway pressure) but also contraction of upper airway muscles to keep the
pharynx patent. Particularly during REM sleep, loss of activity of the upper airway muscles allows inspiratory collapse of the soft tissues and obstruction of the
upper airway. Airflow eventually resumes because of microarousals (not evident to the patient) when activity of the upper airway muscles is restored. Cycle
repeats itself. During an episode of central apnea monitoring of chest wall motion reveals no movement, corresponding to cessation of airflow and a fall in O 2
saturation. With obstructive apnea, chest wall and abdominal movement can be detected during a futile attempt to move air through the obstructed airway.
Airflow measured simultaneously is found to be absent (V T = 0) and O2 saturation drops to profoundly low levels. Respiratory depressants (alcohol and
sedative-hypnotic drugs) worsen obstructive sleep apnea. First line therapy is nasal Continuous Positive Airway Pressure (CPAP). Compressor maintains
positive pressure in the upper airway throughout the respiratory cycle which functions as a pneumatic splint to keep the airway open.
DISORDERS OF THE RESPIRATORY PUMP

DISEASE
Obstructive
Parenchymal Restrictive
Extra-parenchymal Restrictive (Neuromuscular Weakness)
Extra-parenchymal Restrictive (Chest Wall Deformity)

TLC

FRC

RV

(a)
N

VC

FEV1/FVC

N (or)
(a)
N

MIP = Maximal Inspiratory Pressure; (a) = Depends on expiratory muscle strength

MIP
N
N

ed TLC means restrictive pattern. All lung volumes symmetrically reduced (TLC, RV, FRC & VC all equally ed) + low DL means ILD (restrictive).
Relatively preserved (or) ed RV + normal DL means poor patient effort (or) neuromuscular (or) chest wall disease (restrictive). FRC is not dependent on
the use of respiratory muscles (FRC is determined by inward elastic recoil of the lung balanced by the outward elastic recoil of the chest wall). To achieve
TLC (or) RV the patient must make an effort. This is not the case with FRC. If the FRC is normal it means the elastic properties of the lung & chest wall are
normal. TLC is dependent on the health of the inspiratory muscles & RV is dependent on the health of the expiratory muscles. TLC, RV, FRC & VC are the
volumes that are medically important. TLC = RV + VC. RV = TLC VC. VC = TLC RV.
[1] Neuromuscular Disease : GBS (Usually reversible) / MG (potentially reversible) / poliomyelitis / postpolio Syndrome (occurs decades after the initial
episode of poliomyelitis & involves the same muscle groups) / ALS / muscular dystrophies / quadriplegia / polymyositis. Shallow frequent breaths ed
alveolar ventilation CO2 retension (a greater proportion of each breath is wasted on ventilating the anatomic dead space). Ineffective cough / recurrent
respiratory tract infections / accumulation of secretions areas of collapse or atelectasis. Hypoventilation CO2 retension & hypoxemia. PFTs = restrictive
pattern (ed TLC because of inspiratory muscle weakness). RV is ed because of expiratory muscle weakness. Maximal Inspiratory Pressure (MIP) and
Maximal Expiratory Pressure that the patient can generate (with maximal inspiratory and expiratory efforts) is ed. FRC is near normal. A-a O2 difference is
normal if hypoventilation is the sole cause (but atelectasis & secretions usually add a component of V-Q mismatch or shunt). Note that the compliance of the
lung and the chest wall may be secondarily ed further contributing to the restrictive pattern (the former because of alveolar collapse resulting from shallow
tidal volumes & the latter from stiffening of the chest wall over time). Muscle weakness is however the primary cause of the restriction.
[2] Diaphragmatic Disease: If the diaphragm is required to perform an excessive amount of work (obstructive & chest wall diseases) or if its energy supplies
are limited (ed CO / anemia / hypoxemia) diaphragmatic fatigue may develop. When a superimposed acute illness further increases the WOB or when an
intercurrent problem decreases the energy supply available to the diaphragm hypoventilation respiratory failure. Inefficient diaphragmatic contraction is
another factor that contributes to diaphragmatic fatigue (especially in patients with obstructive lung disease). When the diaphragm is flattened and its fibers
are shortened as a result of hyperinflated lungs, the force developed during contraction is less. A higher degree of stimulation is necessary to generate
comparable pressure by the diaphragm, and increased energy consumption results. MIP is ed. Diaphragmatic weakness can be demonstrated in the supine
position by the abdomen moving paradoxically inward during inspiration (absent diaphragmatic contraction PIP falls because of contraction of other
inspiratory muscles -ve PIP sucks in the diaphragm & abdominal contents). Assisted ventilation with a mechanical ventilator to rest the diaphragm is one
potential method for reversing fatigue. The 3 causes of diaphragmatic fatigue are underlined. The same principles apply to unilateral (or) bilateral
diaphragmatic paralysis. U/L Diaphragmatic Paralysis: With rapid inspiratory activity the normal diaphragm contracts and therefore descends while the
paralyzed diaphragm moves passively and paradoxically upward as a result of rapid development of negative intrathoracic pressure (real-time observation
under fluoroscopy). B/L Diaphragmatic Paralysis: Patient depends on the accessory muscles of inspiration to maintain minute ventilation. There is severe
orthopnea (when the patient is supine, the abdominal contents push on the flaccid diaphragm). Paradoxical inward motion of the abdomen during inspiration
when they are supine. VC when supine << VC when erect.
[3] Chest Wall Diseases (Kyphoscoliosis): Stiff rib cage that is difficult to expand (ed chest wall compliance). Greater change in pressure is required to
achieve a given change in volume. This es the work of breathing. e in VT & e in RR es wasted ventilation and alveolar ventilation falls. As this pt ages
the chest wall compliance will further e. FRC is ed because the poorly compliant chest wall has a ed capacity to recoil outwards. TLC & VC are also ed.
RV relatively preserved. ed TLC itself means a restrictive pattern. The marked distortion of the chest wall causes underventilation of some regions of the
lung microatelectasis V-Q mismatch. Therefore the 2 causes of hypoxemia here are hypoventilation & V-Q mismatch. Hypoxemia HPV pulmonary

hypertension corpulmonale. Hypercapnia. Exertional dyspnea = MC Sx. Expiratory muscle function is preserved / an effective cough is maintained /
problems with secretions & recurrent respiratory infections are not prominent clinical features (unlike pts with neuromuscular disease). End results are chronic
respiratory failure (with ing hypoxemia & hypercapnia) & cor-pulmonale.

[4] Obesity: Chest wall stiffer because of more soft tissue + large abdomen pushes the diaphragm upwards to a higher resting position. ed chest wall
compliance. Lower tidal volumes and ed RR ed wasted (or) dead space ventilation (means ed alveolar ventilation). Some pts e their overall minute
ventilation to maintain alveolar ventilation & PCO2 remains normal. If compensation is defective there will be hypercapnia. This is called pickwickian syndrome
(or) obesity hypoventilation syndrome (includes peripheral edema related to cor-pulmonale and RV failure). Hypercapnia could be related to resp. muscle
fatigue. Pts without hypercapnia are said to have simple obesity. High diaphragm (low FRC) causes closure of airways & alveoli at the lung bases regional
hypoventilation V/Q mismatch Hypoxemia. Obesity + depressed respiratory drive + respiratory muscle weakness + obstructive sleep apnea syndrome
contribute to the respiratory dysfunction. Complications = pulmonary hypertension / corpulmonale / RV failure (all because of hypoxemia during the day &
night). PFTs frequently demonstrate a restrictive pattern, with a decrease in TLC. FRC & VC ed, but RV is relatively preserved. ed PaO2 & ed A-a O2
gradient (because of V-Q mismatch). In pts with hypercapnia there is superimposed hypoventilation. If patients have sleep apnea syndrome - ABG values
become even more deranged at night during episodes of apnea.

The diaphragm is longer at the end of expiration (FRC) and at this position tension generated is higher
(akin to frank-starling for the heart)
Impaired Mucociliary Clearance: Cough includes
[1] Deep inspiration to near TLC
[2] Increase in intrathoracic pressure against a closed glottis
[3] Glottis opens suddenly pressure in the airways falls rapidly explosive expiration (with high linear airflow velocities) carry the irritant along with
mucus out of the respiratory tract.
Paralyzed diaphragm = cannot take a deep breath; weak expiratory muscles (quadriplegia) = cannot generate a large increase in intrathoracic pressure;
chronic tracheostomy / paralyzed vocal cords = cannot effectively close the glottis. All these patients are prone to respiratory tract infections.
Causes of impaired mucociliary clearance:
[1] Dyskinetic Cilia Syndrome (Immotile Cilia Syndrome): Absence of dynein arms on the microtubules. Chronic sinusitis / chronic bronchitis / bronchiectasis
poor sperm motility and infertility (sperm tail has a structure similar to cilia). Kartageners syndrome = triad of chronic sinusitis + bronchiectasis + situs
inversus (variant of the dyskinetic cilia syndrome). Ciliary motion in a specific direction is responsible for proper rotation of the heart and positioning of
intraabdominal organs during embryogenesis.

[2] Viral Respiratory Tract Infection: One of the mechanisms by which viral respiratory tract infections predispose to complicating bacterial superinfections.
[3] Cigarette smoking: Also includes atmospheric pollutants such as sulfur dioxide (SO 2), nitrogen dioxide (NO2), and ozone (O3)
[4] 90% to 100% inhaled O 2 for more than several hours
[5] General anesthesia: with inhalational drug administration during surgery (short-term cilia dysfunction) and contributes to the increased risk of pneumonia
during the postoperative period.
[6] Mechanical ventilation: Endotracheal tubes pose a significant risk for bacterial infection of the lower respiratory tract (ventilator-associated pneumonia) in
part by preventing glottic closure (required for an effective cough) & also provides a direct conduit into the trachea for any bacteria that have colonized the
endotracheal tube.
Pathophysiology of Pneumonia: Lobar Pneumonia: tends to spread throughout an entire lobe. Spread of infection occurs from alveolus to alveolus through
inter-alveolar pores (pores of Kohn). Dense consolidations. Bronchopneumonia: distal airway inflammation is prominent along with alveolar disease, and
spread of infection tends to occur through airways. Patchy in distribution. Interstitial Pneumonia: inflammatory process within the interstitial walls rather than
the alveolar spaces. Viral pneumonias classically start as interstitial pneumonias. Gas-Exchange: Inflammation & infection involving the distal air spaces
decrease in ventilation to the affected areas if perfusion is relatively maintained low V-Q ratios in the diseased regions hypoxemia. When alveoli are
totally filled with inflammatory exudate, there may be no ventilation to these regions and extreme V-Q inequality (shunt) results. Although frank shunting
explains part of the hypoxemia, V-Q mismatch with areas of low V-Q ratio is a more important factor. CO2 retention is not a feature of pneumonia unless the
patient has underlying COPD. Infact patients with pneumonia hyperventilate and are hypocapnic. In TB oxygenation tends to be preserved because V & Q
are destroyed simultaneously in the affected lung.
RESPIRATORY FAILURE: Defined as inability of the respiratory system to maintain adequate gas exchange. In a previously normal individual PaO2 < 60
mmHg (or) PaCO2 > 50 mmHg is considered evidence for acute respiratory failure. In the individual with pre-existing lung disease acute respiratory
failure is defined as a significant change from the pts. baseline gas-exchange status (a COPD pt. lives at 50:50, but cannot be considered to have acute
respiratory failure since this is a chronic process). The pH can provide a clue about whether the pts CO 2 retention is acute or chronic. Because of limited
pulmonary reserve, patients with pre-existing pulmonary disease are at ed risk of acute respiratory failure either from an intercurrent illness (like pneumonia)
or from transient worsening of their underlying disease.
Signs & Symptoms: are because of hypoxemia (or) hypercapnia (or) both. Dyspnea / impaired mental status to stuporous / tachypneic / tachycardic /
restlessness / cyanosis (with severe hypoxemia) / lung findings (of the specific disease). With hypercapnia there is: dilation of cerebral blood vessels
papilledema & headache. The 2 Categories of ARF are Hypoxemic Type & Hypercapnic / Hypoxemic Type.
Hypoxemic Respiratory Failure: Hypoxemia is the major problem & PCO2 is normal or even low. Examples are ARDS & pneumonia. ARDS: Generalized
increase in fluid within the alveolar spaces as a result of leakage of fluid from pulmonary capillaries & is the consequence of a wide variety of disorders that
cause an increase in pulmonary capillary permeability. The abbreviation ARDS was formerly used for adult respiratory distress syndrome, but acute has
replaced adult because the entity can occur in children as well. Mechanism: V-Q mismatching [alveolus partially filled with fluid (or) secretions occupying
the airway lumen (or) collapse of small airways and alveoli] means low V/Q ratio contributes relatively desaturated blood to the systemic circulation.
When these problems become extreme, ventilation to a region of lung may be totally absent so that a true shunt exists. Although HPV serves to limit
perfusion to an underventilated or a nonventilated portion of the lung, this protective mechanism cannot compensate fully and hypoxemia results. Alveolar
filling with fluid + collapse of small airways and alveoli main reason for V-Q mismatch & shunting in ARDS (In ARDS, CO2 elimination remains adequate at
least early in the course of the syndrome because patients are able to maintain adequate alveolar ventilation by increasing their overall minute ventilation,
even when regions of lung have a high V-Q ratio and thus effectively act as dead space).
Hypercapnic / Hypoxemic Respiratory Failure: Hypercapnia is present. For the respiratory failure to be considered acute, the pH must show absent or
incomplete metabolic compensation for the respiratory acidosis. Hypercapnia is associated with decreased PaO2 because of decreased P AO2. Therefore even
if there is no other reason for hypoxemia, the PaO2 will fall (but usually other problems co-exist). Examples are depression of CNS ventilatory control /
disorders of the chest wall or the neuromuscular apparatus / COPD. Pts usually (but not always) have pre-existing lung disease (chronic respiratory failure)
which makes them more susceptible to decompensation from an acute superimposed problem (called acute on chronic respiratory failure). Examples are
pneumonia in a COPD pt. Mechanism: Not only is the total ventilation per minute important; the relative amount of alveolar versus dead space ventilation, is
also important to ensure proper utilization of inspired gas. If the proportion of each breath going to dead space (V D/VT) increases substantially, then alveolar
ventilation will fall & P CO2 will rise even if total minute ventilation is preserved. Patients have two major reasons for hypoxemia: hypoventilation and V-Q
mismatch. True shunts play a limited role in causing hypoxemia in these disorders (unlike the situation in ARDS). Patients respond well to supplemental O 2
with a substantial rise in PaO2. However administration of supplemental O2 to chronically hypercapnic patients may lead to a further increase in PaCO2.

Frequent precipitants of acute on chronic respiratory failure: respiratory tract infection (MCC) / drugs (sedatives & narcotics) / CHF / less common causes
(pulmonary emboli / ed respiratory secretions / environmental pollutants). Sedatives or narcotics may precipitate hypercapnic respiratory failure by
depressing central respiratory drive in a person whose condition is already marginal. Supplemental O 2 in a concentration not much higher than that found in
ambient air, is administered to raise PaO2 to an acceptable level (i.e > 60 mm Hg). If CO 2 elimination deteriorates then an acute respiratory acidosis is
superimposed on the patients usual acidbase status. If significant acidemia develops or if the patients mental status changes as a result of CO 2 retention,
then some form of ventilatory assistance may be required.

Acute Respiratory Distress Syndrome (ARDS): ARDS is formally defined by the presence of severe arterial hypoxemia and diffuse, bilateral pulmonary
infiltrates that are not attributable exclusively to cardiogenic or hydrostatic causes. Nonspecific result of acute injury to the lung, characterized by breakdown
of the normal barrier that prevents leakage of fluid out of the pulmonary capillaries and into the interstitium and alveolar spaces. Also called noncardiogenic
pulmonary edema (or) shock lung. Fluid normally moves out of the pulmonary capillaries and into the interstitial space but they do not accumulate here
(lymphatic vessels are quite effective in absorbing both protein and fluid that have left the vasculature and entered the interstitial space). If fluid movement
into the interstitium increases substantially or if lymphatic drainage is impeded, then fluid accumulates within the interstitial space, resulting in interstitial
edema. When sufficient fluid accumulates or the alveolar epithelium is damaged, fluid also moves across the epithelial cell barrier and into the alveolar
spaces, resulting in alveolar edema. In cardiogenic (or) hydrostatic pulmonary edema, the permeability barrier is intact & the fluid that leaks out has a very
low protein content. Here the permeability of the capillary endothelial and alveolar epithelial barriers are increased as a result of damage to one or both.
Proteins move out of the intravascular space. The fluid that leaks out has a relatively high protein content often close to that found in plasma.

Important to remember that higher pulmonary capillary hydrostatic pressures result in more fluid leaking through an abnormally permeable pulmonary
capillary endothelium than do lower pressures. LVF + ARDS is very bad to have (permeability defect and the elevated hydrostatic pressure work
synergistically in contributing to leakage of fluid leak out of the pulmonary vasculature).
Etiology: What links the diverse etiologic factors in ARDS is their ability to cause diffuse injury to the pulmonary parenchyma. Rather than a specific disease
ARDS is truly a syndrome resulting from any of a number of etiologic factors.
Inhaled Injurious Agents:
[1] Liquid aspiration = acid gastric contents (esp. when pH < 2.5) chemical burn damaging alveolar epithelium / salt or fresh water in near drowning (fresh
water inactivates surfactant) / aspirated hydrocarbons (also inactivate surfactant).
[2] Toxic gas Inhalation = Nitrogen dioxide (NO2) / smoke (chemical products of combustion) / ammonia gas / High O2 conc when given for prolonged
periods (mechanism of O2 toxicity is believed to be generation of free radicals) / overdistention (or) cyclic opening and closing of alveoli induced by
mechanical ventilation.
[3] Bacterial pneumonia (MCC) / Pneumocystis jiroveci pneumonia (esp. in pts with AIDS) / viral pneumonias
Circulating Injurious Agents:
[1] G- sepsis (endotoxin)
[2] Shock (accompanied by other etiologic factors) was previously called shock lung. By itself, insufficient to cause ARDS.
[3] Disseminated intravascular coagulation (DIC)
[4] Fat embolism & amniotic fluid embolism = directly toxic to endothelial cells of the pulmonary capillaries
[5] Drug-induced pulmonary edema = heroin pulmonary edema / other narcotics & sedatives
[6] Acute pancreatitis = enzymes released into the circulation from the damaged pancreas directly injures the pulmonary parenchymal cells
[7] Neurogenic pulmonary edema = Intra-cerebral hemorrhage associated with raised ICT / after generalized seizures / head trauma. Mechanism of
neurogenic pulmonary edema: ed ICT intense sympathetic nervous system discharge extremely high pulmonary capillary pressures mechanical
damage to the endothelium.
[8] Trauma & multiple blood transfusions
Pathology: 2 phases. Exudative Phase: The initial injury in ARDS affects type I alveolar epithelial cells (the cytoplasmic processes of which provide most of
the surface area lining the alveolar walls), capillary endothelial cells or both. Fluid & Inflammatory cell infiltrate in the interstitium & alveolar lumen proteinrich alveolar exudates inactivate surfactant (decreased surfactant production also results from injury to alveolar type II epithelial cells) form hyaline
membranes (represent the protein-rich fluid that has deposited on the alveolar surface). Not associated with homogeneously affected alveoli (rather with
heterogeneous patchy disease). Proliferative Phase: After 1-2 weeks the alveolar type II cells replicate in an attempt to replace the damaged type I cells. In
some cases, the damaged lung parenchyma is not repaired but goes on to develop significant scar tissue (fibrosis).
Mechanical Properties of the Lung: The net result of having fewer effectively functional alveoli (because of flooding) is that less volume enters the lung for
any given inflation pressure & by definition this means that the compliance of the lung is decreased (like having 1 lung). The volume of gas contained within
the lungs at FRC is significantly ed. Rapid shallow breathing.
Gas-Exchange: There is perhaps no better example of shunting than ARDS. Alveolar flooding effectively prevents ventilation of affected alveoli even
though perfusion is relatively preserved causing shunting and hypoxemia. V-Q mismatch also exists (from an uneven distribution of pathologic process within
the lungs). ed surfactant extensive collapse of alveoli. In terms of oxygenation, both V-Q mismatch (with regions of low V-Q ratio) and true shunting
(V-Q ratio = 0) are responsible for hypoxemia. Supplemental O 2 improves whatever component of hypoxemia is due to V-Q mismatch, but it is ineffective for
true shunting. Patient typically does not have hypercapnia except in the terminal stages of the disease. Even though substantial amounts of dead space is
present (as part of the overall V-Q mismatch) the patient is able to compensate by increasing total ventilation. Pulmonary vascular resistance es because of
HPV / fluid in the interstitium (increases interstitial pressure resulting in an increase in resistance of the small pulmonary vessels) / lumen of small vessels are
compromised by microthrombi. This process is however not uniform resulting in V-Q mismatching.
Clinical: After the initial insult (whatever it may be) there generally is a lag of approx. 1 day before the first respiratory symptom (dyspnea) manifests. At this
time the pt. will be tachypneic / the CXR may not reveal significant findings / ABGs however will reveal disturbance of oxygenation (ed AaDO2). Alveolar
ventilation frequently is increased so that PaCO2 is ed (respiratory alkalosis). As fluid and protein continue to leak from the vasculature into the interstitial and
alveolar spaces Rales / CXR reveals extensive interstitial & alveolar edema. Because true shunting of blood across non-ventilated alveoli is important in
the pathogenesis of hypoxemia PaO2 may be relatively unresponsive to supplemental O2. PCWP can distinguish whether the pulmonary edema is
cardiogenic or noncardiogenic in origin. Failure of other organ systems besides the respiratory system is common.
Acute Lung Injury (ALI) = a similar process of lung injury in which the disturbance in oxygenation is less severe (ARDS represents the more severe end of
the spectrum).

MANAGEMENT OF ACUTE RESPIRATORY FAILURE

Goals for Optimizing O2 Delivery to Tissues:
[1] SaO2 > 90% (PaO2 > 60 mmHg): Hb is approximately 90% saturated at a PaO2 of 60 mmHg. Increasing PaO2 to this level is important, but a PaO2 much
beyond this level does not significantly increase the O2 content of blood. Patients with respiratory failure often are maintained at a PaO2 slightly higher than 60
mmHg to allow a margin of safety for any PaO2 fluctuation.
[2] Acceptable Hb level (> 10 gm/dL) corresponding to a hematocrit of > 30%). Blood transfusions will raise the Hb level and O 2 content.
[3] Near-normal CO. PEEP used to improve PaO2 may have a detrimental effect on CO thereby ing O2 delivery to tissues.
Achieving an acceptable pH value & not a normal PCO2, is the primary goal in managing respiratory failure and impaired elimination of CO2. In
patients with chronic hypercapnia (and metabolic compensation), abruptly restoring P CO2 to normal (40 mmHg) may cause significant alkalosis (and thus risk
precipitating arrhythmias or seizures).
Principle of Management: In Acute Respiratory Failure the goal of supportive therapy is to maintain adequate gas exchange until the patient recovers from
the acute illness. The principles for supportive therapy differ considerably in the two main categories of acute respiratory failure. In pts with hypercapnic /
hypoxemic respiratory failure (which is usually acute on chronic) oxygenating the pt. is easy and mechanical ventilation is required only when CO 2
retension es. On the other hand in pts with hypoxemic respiratory failure the problem lies in oxygenating the pt. (because of shunting) and mechanical
ventilation (in the form of PEEP) is required to correct the hypoxemia. In the latter group CO 2 retension is not a major problem.
Treatment of Hypercapnia: Most pts. with acute CO2 retension already have some degree of pre-existing chronic CO 2 retention and their acute problem is
rightly termed acute on chronic respiratory failure. Examples include COPD / chest wall disease / and neuromuscular disease. Hypercapnia may be only
acute (ingestion of drugs in a suicide attempt / severe asthma).
Indications for mechanical ventilation in hypercapnic / hypoxemic respiratory failure:
1) pH < 7.257.30
2) Impaired Mental Status
3) VC < 10 ml/kg (to detect acute RF or serially to detect impending RF)
4) Maximal Inspiratory Pressure (MIP or Inspiratory Force) < 25 cm H 2O negative pressure
5) Other criteria to consider are: nature of underlying disease / speed of disease progress / presence of other medical problems
ed pH & mental status abnormalities are because of CO2 retension and serve as an indirect guide to the patients ability to maintain adequate CO 2
elimination. VC & MIP are useful to detect acute respiratory failure (or) when measured serially to detect impending respiratory failure. These measurements
are most useful in following patients with progressive neuromuscular weakness (ALS) to determine when mechanical ventilation may be necessary.
Treatment of Hypoxemia: In most cases of acute on chronic respiratory failure (hypercapnic / hypoxemic respiratory failure), V-Q mismatch and
hypoventilation are responsible for hypoxemia. For these mechanisms of hypoxemia supplemental O 2 is quite effective in improving the Pa O2, and particularly
high concentrations of inspired O2 are not necessary. Frequently, O 2 can be administered by face mask or by nasal prongs to provide inhaled concentrations
of O2 not exceeding 40% and patients are able to achieve a PaO2 greater than 60 mmHg. Note that the PCO2 may further rise when they receive supplemental
O2 and in that case they may require mechanical ventilation.
In hypoxemic respiratory failure such as ARDS V-Q mismatch and shunting are responsible for hypoxemia. If the proportion of shunt is large then
supplemental O2 is relatively ineffective at raising PaO2. In these cases, patients may require inspired O2 concentrations of 60% to 100% and may still have
difficulty maintaining a PaO2 > 60 mmHg. Such patients with ARDS also require mechanical ventilation but for a different reason than patients with acute on
chronic respiratory failure. Indications for mechanical ventilation in hypoxemic respiratory failure: Inability to achieve a PaO2 of 60 mmHg on
supplemental O2 readily administered by face mask (generally in the range of 40%60%). Benefits of mechanical ventilation for ARDS include: More reliable
administration of high concentrations of inspired O 2 (than through a face mask) / more reliable tidal volumes than those achieved spontaneously by the
patient (poorly compliant lungs of ARDS promote shallow rapid breathing) / allows the use of PEEP . PEEP is effective in ARDS by increasing FRC because
many small airways and alveoli that formerly were closed (microatelectasis) and received no ventilation are opened and capable of gas exchange.
Microatelectasis results from: fluid occupies alveolar spaces thus inactivating surfactant / low tidal volumes / decreased production of surfactant. Lung
compliance is ed & FRC is ed. Therefore PEEP reduces shunting in ARDS. When the shunt fraction is decreased by PEEP, supplemental O 2 is much more
effective at elevating the patients PaO2. The concentration of inspired O 2 then can be lowered and the patient is less likely to experience O2 toxicity
from extremely high O2 concentrations.
es WOB: Mechanical ventilation (ventilatory assistance) in the patient with respiratory failure is important not only for the temporary support of gas exchange
but also for the mechanical support of inspiration, allowing the respiratory muscles to rest thus reducing the WOB. Fatigued respiratory muscles are allowed
to recover, and the relatively large amount of blood flow required by overworking respiratory muscles can be shifted to perfusion of other organ systems. In
the case of COPD (acute on chronic respiratory failure) the flat mechanically disadvantaged diaphragm must cope with an increase in airway resistance. In
neuromuscular disease respiratory muscle strength is insufficient to handle even the normal work of breathing. In ARDS the noncompliant lung increases the
WOB even though respiratory muscle strength is intact.
MECHANICAL VENTILATION
Positive pressure devices. Most commonly, the ventilator is used in a volume-cycled fashion, meaning that each inspiration is terminated and passive
expiration allowed to occur after a specified tidal volume has been delivered by the machine (more reliable in delivering constant, specifiable tidal volumes
than is pressure-limited ventilation). In contrast, in pressure-limited inspiration is terminated and passive expiration allowed to occur after a targeted airway
pressure has been achieved (minimizes the risk of complications from high pressure delivered by the ventilator). An important option available for the
intubated patient with hypoxemic respiratory failure (especially when it is due to ARDS) is PEEP (airway pressure at the end of expiration does not fall to zero
but remains at a pre-determined level). A variation of PEEP that works on the same principle is continuous positive airway pressure (CPAP). The term CPAP
is used when the patient is breathing spontaneously (no positive pressure is provided by a mechanical ventilator) and expiratory tubing is connected to a
PEEP valve. The patient can be either intubated or given a tightly fitting face mask. With PEEP or CPAP: positive pressure within airways and alveoli at the
end of expiration FRC is increased by the positive pressure closure of airways and alveoli at the end of expiration is diminished.
Protective Open Lung Strategy: Used in the treatment of ARDS & complicated cases of acute respiratory failure.
[1] Sufficient PEEP is given to diminish airway & alveolar closure during expiration. PEEP es the shunt fraction & es dead space. Magnitude of former is
greater thereby ing PaO2.
[2] Relatively low tidal volumes (6 mL/kg) are used to protect the lung from volutrauma during inspiration. PaCO2 may rise when relatively low tidal volumes are
used but the elevation in PaCO2 is considered acceptable according to a strategy of permissive hypercapnia.
When the underlying problem that precipitated the need for mechanical ventilation has improved, ventilatory support is discontinued after a successful
spontaneous breathing trial. During the spontaneous breathing trial a rapid shallow breathing index [ratio of the RR divided by V T (expressed in liters)] less
than 105 is predictive of successful weaning.
[1] Low lung volumes (most ARDS pts have ed elastic lung recoil & ed FRC) airway closure in dependent lung regions absorption atelectasis. +ve
pressure es the FRC ed lung volumes. Compliance is ed.
[2] Reduces shunt by keeping flooded or collapsed alveoli open.
[3] Allows P IO2 to be ed ed O2 toxicity
[4] Allows removal of retained secretions by suction &
[5] Helps prevent aspiration

Complications of Intubation & Mechanical Ventilation

[1] Intubation can be complicated acutely by arrhythmias / laryngospasm / malposition
[2] Ulceration (pressure necrosis) of larynx / trachea scarring laryngeal / tracheal stenosis. To decrease these complications, tubes are made with cuffs
that minimize the pressure exerted on the tracheal wall. For prolonged ventilatory support (weeks to months), a tracheostomy tube is preferred over
orotracheal or nasotracheal intubation.
[3] Ventilator-associated pneumonia (because of impaired upper airway clearance mechanisms / aspiration of oropharyngeal secretions around the
endotracheal tube / bacterial contamination of the endotracheal tube or the ventilator circuit.
[4] Barotrauma (or) Volutrauma: pneumothorax or pneumo-mediastinum (high alveolar pressures alveolar overdistention with rupture). Pneumothorax in pts
receiving mechanical ventilation ventilator continues to deliver gas under positive pressure gas enters the pleural space through the rupture PIP es
tension pneumothorax results severely es VR & CO rapid cardiovascular collapse. Catastrophic consequences if not detected and treated quickly.
Especially problematic in the setting of obstruction (asthma or COPD): high levels of PEEP (or) large V T air trapping / pneumothorax / pneumomediastinum & severe hypotension. Air from ruptured alveoli track into the interstitium of lung mediastinum subcutaneous tissues of neck (called
Interstitial Emphysema).
[5] The e in vascular resistance in normal lung regions associated with +ve pressure ventilation tends to redirect blood flow to abnormal lung regions thereby
increasing shunting and ing PaO2.
[6] High levels of PEEP damages the very thin blood-gas barrier in certain regions of the lung (stress failure) pulmonary edema & ARDS. Lowest
pressure consistent with an acceptable PaO2 level should be used.
[7] Decreases CO (+ve intra-thoracic pressures will e VR). More likely to occur with PEEP & if blood volume is ed. PO2 of mixed venous blood depends on
both the CaO2 & CO (provided O2 consumption is constant) and therefore is a good guide to the optimal level of PEEP (rather than CO alone or Pa O2 alone).
CO can be ed with I.V fluids which help restore venous return. Another reason for the decreased CO is PVR es (secondary to the ed alveolar pressure)
ed workload placed on the RV RV output falls.
[8] Diseased alveoli are open during inspiration and collapse during expiration and are therefore subject to further stresses during the repetitive process of
opening and closing (atelectrauma). PPV (without PEEP) es atelectrauma. PEEP (by keeping the alveoli always open) es it. The more normal alveoli are
at risk for overdistention. Both alveolar overdistention and atelectrauma may cause injury to the alveolar wall leading to ARDS. Avoid both alveolar closure
(atelectasis) during expiration by the use of PEEP (and) overdistention during inspiration by limiting tidal volume to 6 mL/kg (or) distending pressure to no
more than 30 cmH2O.
[9] es the alveolar dead space. Compression of capillaries by ed alveolar pressure (zone 1). Also es anatomical dead space because of ed lung volume
leading to ed radial traction on the airways. Physiological dead space is ed.

Non-Invasive Ventilatory Support for Acute Respiratory Failure: Positive pressure is provided through a tightly fitting mask placed over the face. Has
been used for support of patients with cardiogenic pulmonary edema, acute exacerbation of COPD & patients who are not considered suitable candidates for
intubation. Not appropriate if patients are unable to protect their airway & is most useful when the respiratory failure most likely is readily reversible and
therefore of short duration. Does not require use of an endotracheal tube (therefore avoids patient discomfort from the tube itself / injury to the airway mucosa
/ development of lower respiratory tract infection).
Treatment of Chronic Respiratory Failure: In patients with chronic respiratory insufficiency, the goal is to maximize the patients function / minimize
symptoms / avoid cor-pulmonale on a long-term basis. For patients with chronic, irreversible disease who require continuous long-term ventilatory support
positive pressure ventilation via a tracheostomy tube is suitable. A subgroup of patients with chronic respiratory insufficiency (chronic neuromuscular or chest
wall disease accompanied by chronic hypercapnia) do not require continuous ventilatory support but benefit from nocturnal assistance with ventilation.
Rationale for using nocturnal ventilatory support is to allow their inspiratory muscles to rest during the night so they are able to better handle the work of
breathing during the day, and daytime hypercapnia may be improved. Can be provided by positive pressure through a mask or by a device that produces
intermittent negative pressure around the chest wall. Negative-pressure ventilatory support devices have been used most frequently for patients with chronic
respiratory failure resulting from neuro-muscular disease such as muscular dystrophy.
+

--

Role of the lung in acid-base balance: CO2 generated by metabolism es H . CO2 + H2 O H2CO3 H + HCO3
+
+
Elimination of CO2 reduces H (equilibrium left shifted) Respiratory Alkalosis. Retension of CO2 increases H (equilibrium right shifted) Respiratory
Acidosis. Compensation to respiration-induced pH changes is done by the kidney and takes 2-3 days. Compensation for non-respiration induced pH changes
happens immediately. Examples of respiratory acidosis = COPD; sedatives; ALS / MS / GBS; airway obstruction; ARDS.

3 main categories of information can be obtained with routine PFTs:

1. Lung volumes
2. Flow rates (maximal flow within the airways)
3. Diffusing capacity
Flow Rates: With airflow obstruction FEV1/FVC may be N (or) ed; ed TLC; FEF25%-75% is ed; RV/TLC ratio is ed; characteristic configuration of the flowvolume curve (decreased flow relative to lung volume, accompanied by a scooped out or coved appearance to the descending part of the expiratory curve).
FEF25%-75% is a sensitive test & is considered a marker for early or mild airflow obstruction, theoretically reflecting small airway disease. With restrictive
defects the volumes are decreased (narrowing of the curve along the volume (or) x-axis) and flow rates are relatively preserved. The flow rates often appear
increased relative to the small lung volumes producing a tall & narrow curve. DL should be corrected for the patients Hb level.

Patient 1: All measurements of lung volume (TLC, VC, FRC, RV) are decreased, indicative of restrictive disease. FEV 1 and FVC are decreased because of
the low lung volumes, but FEV1/FVC is not ed. This finding along with the fact that FEF25%-75% is also not decreased indicates that there is no obstruction. DL
is decreased, suggesting that the restrictive disease is secondary to an abnormality of the pulmonary parenchyma rather than chest wall or neuromuscular
disease. The flow-volume curve is tall and narrow, consistent with a restrictive pattern. Diagnosis: Interstitial Lung Disease (pulmonary sarcoidosis)

Example 2: FEV1 and FVC are both decreased. Because FEV1 is decreased more than is FVC FEV1/FVC is decreased. FEF25%-75% also is decreased.
These values are indicative of obstruction. TLC is normal, and RV and FRC are increased. The high RV/TLC ratio indicates there is air trapping as is
expected with obstruction. The DL is decreased, reflecting loss of alveolar-capillary bed. The flow volume curve shows an obstructive pattern, characterized
by a striking decrease in flow rates, well seen throughout most of the expiratory curve after the initial peak flow rate. This combination of significant airflow
obstruction with normal or increased volumes and a low DL suggests emphysema. Diagnosis: Emphysema

Example 3: TLC and FRC are reduced, indicating restrictive disease. RV is relatively preserved. FEV 1 and FVC both are decreased, but FEV1/FVC ratio is
preserved. There is no evidence for co-existing obstructive disease. D L is normal, suggesting that the alveolar-capillary bed is preserved. The flow-volume
curve is relatively tall and narrow, without any evidence of obstructive disease. Diagnosis: Extra-parenchymal Restrictive (Chest Wall Deformity =
Kyphoscoliosis)
Analysis of Oxygenation:
1) If the patient is hypoxemic, PCO2 is elevated & AaDO2 is normal (<15 mmHg on room air in a young person, although it increases with age), then
hypoventilation is the cause of the hypoxemia.
2) If the patient is hypoxemic, PaCO2 is normal or low, and AaDO2 is ed, then either V/Q mismatch or shunting is present. With V/Q mismatch, the
pts PaO2 has a good response to supplemental O2. With a true shunt PaO2 does not rise much with supplemental O 2 (even with 100% O2).
3) If the patient is hypoxemic, PCO2 is high, and AaDO2 is increased, then the patient has both hypoventilation (and) either V/Q mismatch or shunt as
the cause of low PaO2.
Miscellaneous Stuff:

Causes of 2 Pulmonary Hypertension: COPD (lung parenchyma destroyed) / Mitral Stenosis / Recurrent Thromboemboli (ed cross sectional area
of pulmonary vascular bed) / L R Shunt / Autoimmune Diseases like SLE (Inflammation Intimal fibrosis & medial hypertrophy) / Sleep apnea
(or) high altitude residence (HPV).
Consequence of PH is cor-pulmonale (RV failure secondary to lung disease).
Apex of the healthy lung is the largest contributor of alveolar dead space.
Think of ed V/Q as regional hypoventilation & ed V/Q as regional hypoperfusion. Extremes of the former is called shunt and extremes of the latter
is called dead space.
In children & young adults RV is determined solely by the balance of forces between the chest wall (outward) & lungs (inward). In older pts and in
disease states (emphysema) there is an additional factor that determines RV: the closing volume. Premature airway closure during exhalation is
because of ed elastic lung recoil forces. This is called air-trapping. This air adds to the RV.
Surfactant: es lung compliance (interpose between surface molecules & e the strong inter-molecular forces thereby ing surface tension) /
Prevents spontaneous collapse of the smaller alveoli (as the alveoli gets smaller the density of surfactant molecules e thereby nullifying the
surface tension forces) / Keeps the alveoli dry (surface tension forces have the effect of sucking fluid out of the capillaries. reducing them therefore
prevents interstitial & alveolar edema).
During inhalation, at low lung volumes the compliance is low (curve is flat) because the surface tension is high. It also reflects the recruitment of
collapsed alveoli (re-opening collapsed alveoli requires a high change in pressure = critical opening pressure).
During inhalation, at high lung volumes the compliance is low (curve is flat) because the elastic recoil force of the lung is ed.
Surfactant has a greater effect on compliance of the lung during exhalation than during inhalation (explaining the hysteresis).
Without surfactant the smaller alveoli will collapse shunting hypoxemia. Infant Respiratory Distress Syndrome (or) Hyaline Membrane Disease
(and) Adult Respiratory Distress Syndrome (ARDS). ARDS is associated with a wide range of disorders that cause damage to the alveolar-capillary
interface & alters the function of surfactant.
Air travels in the conducting airways by bulk flow. Bulk flow may be turbulent or laminar depending on its velocity. In the respiratory zone air
movement is by diffusion.
Factors that e airway resistance: bronchoconstriction / ed lung volume / ed density of inspired gas / dynamic compression.
Terminology: Eupnea: normal quiet breathing; Tachypnea: ed RR; Hyperpnea: ed rate & depth; Dyspnea: sensation of breathlessness (or)
labored breathing; Orthopnea: dyspnea while recumbent; Apnea: cessation of breathing
Sleep Apnea: loss of pharyngeal muscle tone during sleep airway obstruction hypoxemia (and in some cases hypercapnea) stimulation of
the respiratory center pt. awakens. No deep (or)REM sleep / daytime fatigue / pulmonary hypertension (because of hypoxia) / RV hypertrophy /
cardiac arrhythmias.
Emphysema pts exhale with pursed lips to e back pressure through the airways, which helps maintain their patency.
The compliance of the lung is greater in the middle pressure & volume ranges. ed compliance = fibrosis / pulmonary edema / ed surfactant.
ed compliance = emphysema / age.
The strong inter-molecular attractive forces in a liquid are called vander-waals forces. At an air-liquid interface there is in-equality of forces (stronger
on the liquid side and weaker on the gas side because of greater distance between molecules in the gas phase). Surface tension causes the

surface to maintain as small an area as possible surface layer is pulled towards the center of curvature of the alveolus. This same force also
tends to suck out fluid from the pulmonary capillaries.
Absent surfactant atelectasis / alveoli filled with transudate / ed lung compliance / V-Q mismatch / ed WOB. All lead to hypoxemia &
hypercapnia.
In COPD pts. there is long standing hypercapnia and adaptation occurs with time. In such patients the ventilatory drive is primarily due to
hypoxemia. Administration of a high O2 mixture blunts the hypoxic drive leading to severe hypoventilation.
Alveolar ventilation & CO (pulmonary blood flow) are both 5 L/min giving a normal V/Q of 1.
Blood flow es more sharply from top to bottom of the lung than does ventilation giving a high V/Q at the apex. Reactivation TB tends to involve
the apex.
Changing PACO2 will change PAO2 by the same amount (If PACO2 es by 40 then PAO2 will e by 40). But the reverse is not true (Changing PA O2 will do
nothing to PACO2). Only in pathology (like chronic hypercapnia / COPD) will the PACO2 change (and this is due to other reasons).
3 factors that affect alveolar O2 are PACO2 / Patm / FIO2.
During exercise body metabolism & alveolar ventilation e proportionately therefore PACO2 remains constant. What increases is the venous PCO2.
All this venous CO2 is washed out by the lung.
Early fetal lung is mostly collapsed because of absent surfactant.
IMPORTANT: Central CO2 receptors adapt, but the peripheral O2 receptors do not adapt. In a chronic CO2 retainer (COPD) the only drive for
ventilation is the low PaO2 acting on the peripheral receptors (because CO 2 receptors have adapted). Giving these guys enriched O 2 will e PaO2
and therefore eliminate their only drive for ventilation stop breathing PaCO2 acidosis disaster.
Remember that with obstruction the problem is usually with expiration & with restriction the problem is usually with inspiration.
Important volumes & capacities are: VT; RV; FRC; VC & TLC
With L R shunts, output of the right heart is > the output of the left heart resulting in elevated pulmonary blood flow & pressures (chronically this
results in pulmonary hypertension). No hypoxemia. Diagnosis is based on where the fist step-up in P O2 (measured using a venous catheter) is
seen: ASD RA / VSD RV / PDA PA.

Patterns of PaCO2 & PaO2 in different types of respiratory failure (Figure 9.3 / John B. West):
A: hypoventilation (neuromuscular disease like poliomyelitis / narcotic overdose)
I: hyperventilation (like in high altitude)
B: severe V-Q inequality. COPD. B F: O2 therapy improves the PaO2 but increases the PaCO2 (O2 depresses the ventilatory drive). Hypoxemia is the
stimulus for ventilation in these patients.
C: advanced diffuse interstitial lung disease. Severe hypoxemia not accompanied by CO 2 retension because of an e in ventilation.
D: ARDS. Severe hypoxemia with a low PaCO2. D E: O2 therapy es the PaO2 but PaCO2 remains low. Hyperventilation in ARDS is due to stimulation of the J
receptors and therfore PaCO2 remains low (until very late) inspite of O 2 therapy.
CO2 retension can therefore be caused by either hypoventilation (or) ventilation perfusion inequality.
SUMMARY OF OBSTRUCTIVE VERSUS RESTRICTIVE PATTERNS

VC

PFT

FRC
RV
TLC
FV Loop
PEF
O2max

Compliance
Stiffness
Recoil
PIP
FEV1
FVC
FEV1/FVC
FEF25-75%
PaO2
PaCO2
pH
DLCO

RD

OD

more ve

less ve

/
/

()
()
()

FEV1 = 4L; FVC = 5L; FEV1/FVC = 80%; FEF25-75% = 4 L/sec; PaO2 = >90; PaCO2 = 40; pH =7.4; DLCO = 25 ml/min/mmHg;
Compliance = 0.20 L/cmH2O. (Within brackets are the values with exercise)
COPD Patient is a 50/50 (i.e PaO2 of 50 mmHg & PaCO2 of 50 mmHg)
FEV1 >200ml (or) >15% improvement in response to bronchodilator therapy is an index of reversibility
RV/TLC = 35% (e indicates air trapping). * = DL will be normal in asthma & chronic bronchitis & ed in emphysema.
FVC & FEV1 usually e when lung function is compromised.
Most Diagnostic: OD: ed FEV1/FVC with ed TLC; RD: ed FVC with ed TLC

2 FACTORS THAT AFFECT PACO2 ARE:

1) ALVEOLAR VENTILATION (= CO)
2) METABOLIC CO2 PRODUCTION (300 ml/min)
3 FACTORS THAT AFFECT PAO2 ARE:
1) ATMOSPHERIC PRESSURE (760 mmHg)
2) FRACTIONAL CONCENTRATION OF INSPIRED O2 (21%)
3) PACO2 (40 mmHg) Changing PACO2 will change PAO2 in the opposite direction by approximately the same amount in mmHg.
Normal values are shown within brackets.
Whenever there is an A-a O2 gradient end-tidal air does not reflect arterial values.
PaO2

Hb Conc.

% Sat

O2 Content

ANEMIA

POLYCYTHEMIA

CO POISONING

With mouth breathing the greatest resistance is in the medium sized aiways & with nose breathing the greatest resistance is in the nasal cavity.
nd
With Inspiration there will be a reflex e in HR (sinus arrhythmia) & Delayed P2 (wide splitting of the 2 heart sound).
In RDS WOB is ed (because of ed lung compliance) / atelectasis of smaller alveoli / pulmonary edema.
Filling alveolus with saline eliminates the air-liquid interface and therefore es surface tension forces.
CO is dangerous for 3 reasons: left shifts the ODC / es the O2 content of blood / inhibits cytochrome oxidase.

O2 a pefusion-limited gas can become diffusion-limited for the following reasons:

1) Thickened blood gas barrier as in fibrosis / interstitial edema
2) ed surface area as in emphysema
3) Intense exercise decreasing the time needed for equilibration
4) Low O2 gas mixture (or) high altitude decreases the O 2 gradient.
Because of 3 & 4 exercising at high altitudes can make O2 diffusion-limited even in normal individuals.