OBJECTIVES:
1. Introduce basic concepts of respiratory system function.
2. Review the gross anatomy and organization of the respiratory system.
3. Review the anatomy and histology of the respiratory zone.
4. Describe the non-respiratory functions of the lung.
I. BASIC CONCEPTS OF RESPIRATORY SYSTEM FUNCTION:
A. Why a respiratory system?
1. Respiratory function: Gas transport for metabolism
2. Non-Respiratory function: Filtering and metabolism
B. Gas transport: Oxygen in and Carbon Dioxide out
1. Ventilation: (atmosphere <-> respiratory zone)
2. Lung diffusion: (respiratory zone <-> erythrocyte/plasma)
3. Circulation: (blood flow carries erthyrocyte/plasma <-> tissue)
4. Tissue diffusion: (erythrocyte/plasma <-> tissue cells)
5. Internal respiration: (cellular metabolism using O
2
& producing CO
2 e.g. Kreb ’s Cycle)
II. VENTILATION: Structure and Function
A. Gas conduction:
1. Upper respiratory tract: Gas humidification, filtration, and warming
2. Conducting airways: Gas distribution to respiratory zone a) Irregular dichotomous branching with 20-28 branches of which first 16-
17 are conducting only (the conductive zone).

Note: The conductive zone only distributes and collects gas. There is no gas diffusion into or out of the body b) The airways maintain patency depending upon structure: i.
Trachea: Cartilage rings ii.
Bronchi: Cartilage plates iii.
Bronchioles: No cartilage -> depend upon lung structure c) Total cross-sectional area of conducting airways INCREASES as we move from the trachea to the respiratory zone.
Note: This occurs because of the number of small airways increases geometrically d) VELOCITY (cm/sec) = FLOW (cm 3 /sec) / CROSS-SECTION AREA
(cm 2 ). Therefore in the periphery of the lung near the respiratory zone gas velocity drops to zero and there is no CONVECTIVE movement of gas.
Movement of gas in the respiratory zone is by DIFFUSION alone. e) Terminal bronchioles of conducting airways have ciliated and goblet cells to help clear particulate matter
f) Respiratory bronchioles mark the beginning of the respiratory zone and have alveoli in their walls.
3. The Ventilatory Pump:

a) Pump Structure: i.
Rib cage and spine ii.
Diaphragm iii.
Intercostal muscles iv.
Abdominal muscles v.
Accessory muscles (Neck and shoulder girdle) vi.
Visceral and parietal pleurae and pleural fluid b) Quiet breathing: Inspiration active and expiration passive, while active expiration in coughing, exercise, loud vocalization and disease. c) Respiratory control is a complex, integrated phenomenon with voluntary and involuntary controls.
III. DIFFUSION: Structure and Function
A. Diffusion: Basic concepts
1. Gas diffusion is PASSIVE from high partial pressure to low partial pressure.
2. Alveolar O2 > Pulmonary capillary O2: O2 diffuses to capillary.
3. Pulmonary capillary CO2 > Alveolar CO2: CO2 diffuses to alveolar gas.
4. FICK'S LAW OF DIFFUSION applied to gases in the lung:

B. The respiratory zone:
1. Respiratory bronchioles, alveolar ducts and alveoli.
2. The zone is designed to maximize efficient gas exchange by diffusion: a) Large surface area: 70 m 2 (300 million alveoli) b) Large volume of gas to maintain diffusion pressure gradient (150ml in conduction zone vs 4,000 ml in respiratory zone) c) Very thin membrane (0.5 micron)
3. Alveolar blood-gas barrier: a) Respiratory epithelium b) Interstitial space c) Capillary endothelium d) Plasma e) Erythrocyte
C. Pulmonary blood flow:
1. All of cardiac output (+/-5%) passes through the respiratory zone.
2. Pulmonary arteries carry blood from the right heart (deoxygenated).
3. Pulmonary arteries distribute blood to the pulmonary capillary system to maximize erythrocyte exposure to alveolar gas tensions.

4. The churning/pumping action of the heart aids in gas diffusion in the respiratory zone.
5. The bronchial vessels arise from the aorta and carry nutrient blood to the airways.
6. Thus the lung is efficiently designed to conduct and distribute gas to a very large, thin diffusion membrane with good blood supply.
D. Hemoglobin & Myoglobin
1. Hemoglogin (Hb)
Tetrametric, two alpha chains and two beta chains
binds a total of 4 oxygen molecules
carries O
2
from lungs to tissues
cooperative binding of O
2
required to increase the solubility of O
2
in blood
2. Myoglobin (Mb)
Monomeric
Binds 1 oxygen molecule.
Carries O
2
from capillaries to sites of usage (mitrochondria) in cells.
Non-cooperative binding of O
2
.
3. Properties of heme group
Example of a prosthetic group
Heterocylic ring containing 4 pyrrole rings
Central atom is Fe 2+ (usual oxidation state)
Fe 3+ in cytrochromes
Mg 2+ in chlorophyll
Proximal histidine is important in transducing the binding event to protein.
O
2
binding induces a change in the electronic state of Fe 2+ that changes its absorbance spectrum.
Oxy Heme
Deoxy Heme

Oxygen Binding to Hemoglobin

The O
2
saturation curve of Hb is
SIGMODIAL .

Such a sigmodial saturation curve is diagnostic of a COOPERATIVE
INTERACTION between the ligand,
O
2
, and the protein.

Initially, Hb is in a low affinity T-
STATE .

Binding of O
2 causes a conformational change in the Hb, which converts it to the high affinity
R-STATE .

Thus the sigmodial saturation curve is a composite of a low affinity and a high affinity curve.

Binding of O
2
causes a conformational change in the Hb, which converts it to the high affinity R-STATE .
The Significance of the Sigmodial Oxygen Binding Curve
1. The significance of the sigmodial O
2
saturation curve of Hb can be appreciated from the graph to the right.
2. While both Mb and Hb will be saturated with O
2 at the partial pressure of O
2
in the lungs, only hemoglobin will release significant amounts of O
2
at the partial pressure of O
2 present in the tissues .
3. In fact, the O
2
released by Hb can then be taken up by Mb for O
2
storage in those tissues, such as muscle, that have significant amounts of Mb.
Hemoglobin Structure and Cooperative O
2
Binding
The differences in O
2
affinity between T-State (deoxy) and R-State (oxy) Hb can be understood in terms of the changes in quaternary structure that accompany the conversion of

deoxy Hb to oxy Hb . o The overall changes can be appreciated from this animation ( oxy5 ). You can distinguish the oxy conformation because of the red O
2
bound to the blue iron. o The shift from the deoxy to oxy conformation arises from the fact that in deoxy Hb the iron lies out of the plane of the heme ring, but when O
2
binding occurs, the iron moves into the plane of the heme ring ( oxy1 ). o Because the proximal His is bound to the Fe, it moves also, causing the helix in which it is found to move ( oxy2 ). o This movement alters the structure of each subunit ( oxy3 ) , which in turn alters the interaction between subunits at the interfaces ( oxy4 ). o This ultimately leads to the shift from the deoxy to the oxy conformation ( oxy5 ). o Because of the way in which the subunits are packed together, one subunit cannot shift from the deoxy to oxy conformation without causing the others to change also, even though the other subunits have not bound O
2
.
The Bohr Effect

In the tissues, the pH is lower due to the presence of CO
2
.

The lowered pH causes Hb to lose O
2
.

This is known as the BOHR EFFECT and increases the delivery of O
2
to the tissues.

The origin of the Bohr effect lies in the fact that deoxy Hb is a weaker acid than oxy Hb:

A major contribution to the Bohr effect involves the C-

In the deoxy state, this His forms a salt bridge to
Asp 94, if the His ring is protonated.

The salt bridge stabilizes the protonated form of the His, causing a high pK a
, in the deoxy state.

Carbon Dioxide Transport

The presence of CO
2
in the tissues alters the affinity of Hb for O
2
in two ways :
1. Through lowering the pH - the Bohr effect
2. Through the formation of carbamates by the amino terminal amino groups of
Hb:
The carbamation reaction releases H + , which favors the Bohr effect and the negatively charge introduced allows formation of additional salt bridges, but only in the deoxy state. Thus, carbamation favors the deoxy state.
Bisphosphoglycerate (BPG)
1.
2.
3.
The red blood cell contains high concentrations of bisphosphoglycerate (BPG), which is an ALLOSTERIC EFFECTOR of Hb's affinity for O
2
.
BPG binds strongly to the deoxy form of Hb, but only weakly to the oxy form.
Thus, BPG favors the deoxy conformation.
The importance of BPG as an allosteric regulator of hemoglobin's O
2
affinity
1. High altitude adaptation
- Adaptation to high altitude is a complex physiological process that involves many events.
- One event that occurs within 24 hours is an increase in the content of BPG in the erythrocyte.
2. The effect of the increased concentration of BPG is to reduce the affinity of hemoglobin for O
2
, which increases the efficiency of O
2
delivery to tissues.
The Physiological Transport of O
2
and CO
2

How do all these allosteric effects combine to allow Hb to carry O
2
from the lungs (gills) to the tissues and to carry CO
2
from the tissues to the lungs (gills)?
As shown below, Hb stripped of all its allosteric effectors has too high an affinity for O
2
to allow effective transport of O
2 to tissues. However, the presence of both CO
2
in the tissues and BPG in the red blood cell create a situation in which O
2
is efficiently transported from lung to tissue.
Summarize :
1. In the lungs the partial pressure of O
2
is high, which overcomes any negative allosteric effects and causes complete oxygenation of Hb.
2. As Hb-O
2
enters the tissues the presence of CO
2
and a lowered pH combine to favor the deoxy conformation and release of O
2
.
3. The presence of BPG aids the delivery of O
2
by favoring the deoxy conformation.
4. Deoxy Hb binds CO
2
.
The deoxy Hb returns to the lungs where the pH is higher, the O
2
content higher and the CO
2 content is lower. All these factors favor reverse of the carbamation reaction, deprotonation of His
146 and the formation of oxy Hb.
Mutant Hemoglobins

Several hundred mutant Hemoglobins are known to exist.

A.

Many of these changes cause no known effect, but several lead to pathologies associated with abnormal O
2
transport.


First, lets look at HbS or sickle cell hemoglobin.
 chain.

This seemingly innocuous change places a hydrophobic sidechain on the surface of the protein.
 of another HbS.

This leads to polymer formation and precipitation of the deoxy HbS.

This leads to red cell lysis and anemia.
Mutant Hemoglobins - what can be learned from experiments of nature?

Mutant hemoglobins provide unique opportunities to probe structure-function relations in a protein.

There are nearly 500 know mutant hemoglobins and >95% represent single amino acid substitutions.

About 5% of the population carries a variant hemoglobin.

Some mutant hemoglobins cause serious illness.

The structure of hemoglobin is so delicately balanced that small changes can render the mutant protein nonfunctional.
IV. NON-RESPIRATORY FUNCTION OF THE LUNG:
A. Basic concepts:
1. The lung performs other functions than gas exchange: a) Maintenance and defense b) Filtering c) Chemical processing
2. Maintenance and defense: a) Protein and connective tissue synthesis b) Surfactant synthesis c) Mucociliary clearance d) Immune function

3. Filtering: The lung is ideally designed to filter the bloodstream of particulate matter (clots, bacteria,
passing that blood on to the body.
4. Chemical processing: a) Production of hormones: ACTH, Prostaglandins, Vasoactive peptides, growth factors, serotonin and others. b) Arachidonic acid metabolites are very potent agents with marked effects upon smooth muscle and inflammatory cells: i.
Damage to the pulmonary endothelium releases
ARACHIDONIC acid from the phospholipid cell membrane
(Phospholipase A). ii.
Lipoxygenase pathway takes arachidonate to leukotrienes. iii.
Cyclooxygenase pathway takes arachidonate to endoperoxides. iv.
These substances have effects in the lung and elsewhere in the body. c) Clearance function: serotonin, norepinephrine, bradykinin, prostaglandins. d) Transformation: Angiotensin I to Angiotensin II.

OBJECTIVES:
1. Describe the lung volumes.
2. Describe the elastic properties of the lung.
3. Discuss the function of surfactant and what occurs in its absence.
4. Describe the elastic properties of the chest wall and its interaction with the lungs.
5. Describe regional ventilation at the apex and base of the lung.
I. THE LUNG VOLUMES:
A useful way to remember the lung volumes is to learn to draw the diagram below and to remember the fact that "capacities" are always made up of "volumes":
A. Volumes:
1. Tidal volume (TV)
2. Residual volume (RV)
3. Inspiratory reserve volume (IRV)
4. Expiratory Reserve volume (ERV)
B. Capacities:
1. Total lung capacity (TLC)
2. Vital capacity (VC)
3. Functional residual capacity (FRC)
4. Inspiratory capacity (IC)

II. ELASTIC PROPERTIES OF THE LUNG
A. COMPLIANCE
1. Compliance = Volume / Pressure (ml / cm H2O):
Assume that the diagrams below represent the lung (sphere and tube) in the chest (box) at the end of an inspiration. If the respiratory muscles relax then the pleural pressure will become less negative and the lung will exhale. If we measure the volume out and the change in pressure we can calculate the compliance:
2. Compliance is greater near FRC (40% of TLC) and lowest near TLC.
3. Specific compliance a) As the lung grows, its compliance increases. Thus, the lungs of adults are more compliant than the lungs of children - and- the lungs of large adults are more compliant than the lungs of small adults. BUT: Adults need to take bigger breaths because of greater metabolic need.

b) We can correct for this by dividing the absolute compliance by lung volume to give the specific compliance:
Specific compliance (1/ cmH2O) = Compliance (L/ cmH2O) / TLC (L) c) While specific compliance is similar between species and from childhood to adulthood, there is a tendency for the specific compliance to slightly decrease from infancy to early adulthood and then to again increase with old age.
4. Tissue forces: a) Elastin and collagen network b) Airway structures c) Pulmonary and bronchial vessels
5. Surface forces and the air-liquid interface:
Water filled lung is more compliant and shows less hysteresis than the air filled lung:
6. LAPLACE EQUATION: b) For the same surface tension, small alveoli (low radius; high pressure) will empty into large alveoli (high radius; low pressure)

c) Surfactant, a complex protein/phospholipid opposes the Laplace law by having low surface tension when surface area is small (i.e. low radius; small alveoli) and a higher surface tension when surface area is large. It is produced by the granular or type-II pneumocytes. d) Surfactant shows HYSTERESIS in its TENSION / SURFACE AREA relationship. e) Premature infants do not have surfactant and develop diffuse alveolar collapse, a disease called respiratory distress syndrome or hyaline membrane disease.
III. ELASTIC PROPERTIES OF THE CHEST WALL
A. At FRC the chest wall is trying to recoil outward, it has been pulled in by the elastic recoil of the lung.
B. At 70% of TLC the chest wall is in balance, and above that it is recoiling inward.
C. At residual volume the chest wall is very stiff, has maximum outward recoil, and is a major determinant of RV
IV. ELASTIC PROPERTIES OF THE LUNG-CHEST WALL SYSTEM
A. The pleura are opposed and slide upon each other with a thin film of pleural fluid.
B. During quiet breathing, the chest wall's outward recoil aids inspiration.
C. Functional residual capacity (FRC) is determined by the balance of the outward recoil of the chest against the inward recoil of the lung.
(Note: Insp recoil causes outward movement (inflation) and Exp recoil causes inward movement (deflation) of the system)

V. REGIONAL VENTILATION OF THE UPRIGHT LUNG AND GRAVITY
A. Pleural pressure gradient.
1. There is a pleural pressure gradient along the vertical distance of the lung of about 0.25 cm H2O per cm of lung such that the apex is more negative.
This occurs because of the weight of the lung. Where there is no gravity
(zero-G ), the pleural pressure is equally negative all over the lung surface. In a gravitational field (on earth) the positive pressure generated by the lung's weight is added to the negative pleural pressure. At the top of the lung (apex) there is no weight to add and the pleural pressure is most negative. At the bottom of the lung (base) the whole weight of the lung is added in causing a less negative pleural pressure. The density of the lung is such that 0.25 cmH2O pressure is added for every 1 cm in height down from the top.
2. This results in the alveoli at the apex being at a higher percent of their maximum volume than the alveoli at base of the lung.
The more negative pressure in the pleural space stretches the apical alveoli more than the less negative pressure at the base does to basal alveoli. Remember, the pressure in the alveoli is atmospheric when there is no flow going on. Since atmospheric pressure is greater then the

negative pleural pressure (by definition) it pushes on the alveolar walls and stretches the alveoli.
B. Regional ventilation:
1. Remember that at higher lung volumes the lung is less compliant, thus the alveoli at the apex of the lung are less compliant than those at the base:
2. In this example the alveoli at the apex only changed 20% of their maximum volume at TLC for a 10 cm H2O pressure change. The alveoli at the base changed 40% of their maximum volume for the same pressure change.
3. During a breath the alveoli at the base will change volume more than those at the apex and thus they will ventilate more than those alveoli at the apex.
OBJECTIVES:
1. Understand the concept of resistance and the difference between the static or elastic properties, and the dynamic or resistive (non-elastic) properties.
2. Describe what resistances make up lung resistance.
3. Discuss turbulent and laminar flow and how the flow regime affects resistance.
4. Describe the distribution of resistance in the lung.
5. Describe the determinants of airway caliber.

I. ELASTIC (STATIC) vs RESISTIVE (DYNAMIC) PROPERTIES OF THE
LUNG:
A. ELASTIC (static) properties relate pressure and volume change:
1. When the lung is stretched by increasing volume a pressure is developed across the lung
(transpulmonary pressure = elastic recoil pressure at that volume).
2. At the end of inflation the lung is held at a given volume and is not changing, i.e. there is no more flow into or out of the lung => it is STATIC.
3. Even though it is STATIC, the elastic recoil generates a pressure which represents energy stored in the elastic structure (tissue and surface forces) of the lung.
4. On deflation, the energy is given back causing gas to flow out of the lung and the recoil pressure to decrease.
5. If the lung is NON-COMPLIANT, i.e. stiff and has a high ELASTANCE then the pressure at end-inflation will be high. If the lung is COMPLIANT than the lung has low ELASTANCE and the pressure at end-inflation will be low.
ELASTANCE = 1 / COMPLIANCE
B. RESISTIVE (dynamic) properties are evident only while the lung is changing volume; i.e. when there is flow into or out of the lung.
1. RESISTANCE describes the energy lost due to the friction and turbulence
(acceleration) of gas when there is gas flow.
2. This loss of energy is measured as a drop in pressure DP across the resistance.
3. RESISTANCE generally obeys Ohm's Law:
4. During exhalation, the elastic recoil pressure (P1 >> P2) stored in the lung drives a flow of gas out of the lung across the resistance of the lung:

5. Corollary: For a given pressure drop, flow is inversely proportional to resistance:
II. RESISTIVE PROPERTIES OF THE RESPIRATORY SYSTEM:
A. Total respiratory system resistance:
1. The are two broad categories of resistance: LUNG and CHEST WALL
RRS = RL + RCW
Where:
RRS = Resistance of the respiratory system
RL = Resistance of the lung (pulmonary resistance)
RCW = Resistance of the tissues of the chest wall
2. Chest wall resistance refers to the energy lost as heat due to friction when the tissues and joints of the chest are displaced during gas flow.
3. Chest wall resistance is a tissue resistance (only about 10% of the total).
B. Pulmonary resistance:
1. Pulmonary or lung resistance is made up of the sum of the resistances of the airway and the tissue resistance of the lung:

RL = Raw + Rtis
Where:
RL = Resistance of the lung
Raw = Resistance of the airway (80% of total lung resistance)
Rtis = Resistance of the tissues of the lung (20% of total lung resistance)
2. As we will see later, Raw is distributed through the airway such that much of the total Raw is in the upper and large central airways.
III. AIRFLOW AND RESISTANCE:
A. Flow regimes in airways:
1. Laminar flow occurs in small airways with low gas velocities and is characterized by a streamlined pattern with a parabolic velocity profile:
Larmina Flow
The "Ohm's law" equation for laminar flow can be written:
3. The radius of the airway is thus critical in determining resistance. If the radius is decreased by 1/2 then the resistance is increased 16 times.

4. Gas viscosity will also increase the resistance; e.g. Helium is more viscous than air and causes increased resistance in those airways with laminar flow.
5. Turbulent flow occurs in larger, central airways with high gas velocities and at branches in airways. It is characterized by complete disorganization of the streamlines with resultant eddies and swirls.
TURBULENT FLOW
6. The Reynold's number (Re) predicts when turbulent flow will predominate. Flow tends to be laminar up until Re > 2000:
7. Under turbulent flow conditions the flow generated is proportional to the square root of the pressure:
8. The constant, K2, varies directly with gas density. Thus the more dense the gas the more energy is lost in turbulence and the greater the pressure drop. Also the pressure drop increases as the square of flow. If flow is doubled then the pressure needed to move the gas increases four times.
9. In many airways, flow is transitional between turbulent and laminar flow:

This is usually written as the total pressure generated by both laminar and turbulent flow:
10. Remember that RESISTANCE = PRESSURE / FLOW therefore dividing by
FLOW
11. Remember: The peripheral airways have a large cross-sectional area and therefore a low gas velocity and hence low Re numbers -> they tend to laminar flow or transitional flow with a large laminar component.
IV. DISTRIBUTION OF AIRWAY RESISTANCE:
A. Upper airway resistance:
1. Mouth, pharynx, and larynx contribute 20-30% of total at rest.
2. With high flow rates (exercise) upper airway may rise to 50%.
B. Lower airway resistance:
1. Because of large increase in total cross sectional area as the bronchial tree branches there is a dramatic drop of resistance after the 4th to 5th generation.
2. Of the total resistance, the small airways make up only 20%.

V. CONTROL OF AIRWAY CALIBER:
A. PASSIVE EFFECTS: Lung volume effects airway caliber in two ways:
1. Larger lungs have larger airways; e.g. an adult has much larger airways than a child -AND- when we take a deep breath the airways stretch increasing heir caliber.
2. We can correct for this by calculating a SPECIFIC RESISTANCE:
SPECIFIC RESISTANCE = RESISTANCE x LUNG VOLUME
3. CONDUCTANCE is the inverse of resistance and is more linearly related to lung volume:
CONDUCTANCE = 1 / RESISTANCE
SPECIFIC CONDUCTANCE = CONDUCTANCE / LUNG VOLUME
4. The relationship between lung volume and conductance or resistance is described by the following graph:
5. Disease like emphysema which decrease lung recoil also decrease the recoil pulling the airways open and cause an increase in airway resistance.

B. ACTIVE EFFECTS: Smooth muscle contraction, mucous production and mucosal edema actively narrow the airways:
1. Smooth muscle tone responds to many stimuli:
2. Chemicals released from mast cells in response to an allergic reaction
(histamines, leukotrienes) also causes airway edema.
OBJECTIVES:
1. Integrate elastic (static) and resistive (dynamic) concepts to understand the energetics of breathing.
2. Discuss the pressures generated throughout the respiratory cycle.
3. Understand the concept of work of breathing and how it can be partitioned into elastic and resistive components.
4. Using work of breathing and its components explain how some ventilatory patterns
(slow, deep tidal volume vs fast, shallow tidal volume) are better in different disease states.
5. Briefly discuss the concept of the time constants of different lung units.
I. ENERGETICS OF BREATHING:
A. Respiratory cycle energetics:
1.
Quiet inspiration is active using the diaphragm and intercostals; energy is stored in the elastic recoil of the lung and expiration is passive relaxation.
2.
During exercise, with voluntary movement, or with disease inspiration may also call into play the accessory muscles which help to stabilize and elevate the rib cage. Expiration may become active with use of the abdominal and intercostal muscles to help force out gas.
B. Pressures during the respiratory cycle:

1. The total pressure exerted across the lung can be described as:
2.
At the end of inspiration and at the end of expiration when there is no flow, the pressure due to resistance must be equal to zero.
3.
At FRC there is a transpulmonary pressure due to the opposing recoil of the lung and chest wall; however, this is at a steady-state and does not require any added energy from the muscles.
4.
As inspiration proceeds, muscle force is needed to generate pressure to overcome the elastic recoil of the lung and to overcome the resistance of the respiratory system.
II. WORK OF BREATHING:
A. The work of breathing is the integral of the V / P curve.
1. Graphically this is represented by the area of the V / P curve:
2. Inspiratory work: ABEFA
3. Inspiratory work is made up of elastic work and resistive work: (a.
Elastic work: ACEFA b. Resistive work: ABECA)
4.
The work done during expiration is the area ACEDA which is the resistive work of expiration and the energy for this comes from the elastic energy stored in the lung (area ACEFA ).

III. OPTIMIZING THE WORK OF BREATHING:
A. An optimal or minimal work of breathing exists for any minute ventilation and any set of respiratory mechanics.
1. Minute ventilation is the total amount of gas moved into and out of the lung in a minute. It is calculated as follows:
MINUTE VENT (L/min) = RESP RATE (1/Min) X TIDAL VOLUME (L)
2.
Thus any given minute ventilation can be met by either a higher tidal volume and lower rate -or- a lower tidal volume and higher rate.
3.
The higher the tidal volume, the higher the ELASTIC work.
4.
The higher the respiratory rate, the higher the flow and RESISTIVE work.
5.
There is an optimum combination of rate and tidal volume to minimize work.
B. How should the two different classes of lung disease breathe to minimize work?
1. OBSTRUCTIVE DISEASE (asthma and emphysema): a) Resistive work is increased because the airways are obstructed b) To reduce resistive work, the patient should breathe with low flows; i.e., the patient should breathe slowly and deeply.
2. RESTRICTIVE DISEASE (pulmonary fibrosis and pulmonary edema): a) Elastic work is increased because the lung is stiff and non-compliant due to scarring (fibrosis) or increased water (edema).

b) To reduce elastic work the patient should breathe with small tidal volumes; i.e., rapidly and shallowly.
IV. TIME CONSTANTS AND REGIONAL VENTILATION:
A. The rate at which a lung unit will fill or empty is inversely proportional to its time constant:
TIME CONSTANT = RESISTANCE X COMPLIANCE
1.
The slowest units will be those which have high resistance and high compliance.
2. The fastest units will be those which have low resistance and low compliance.
3.
Obstructed lungs have long time constants due to increased resistance. This means that they take a long time to exhale.
4.
Restricted lungs have short time constants due to low compliance. This means that they take a short time to exhale.
5.
Communications between lung units help to fill the lung evenly despite units with different time constants.