Jim PierceBi 145b

Lecture 2, 2008-09

How do we describe the normal flow in and out of the mouth, lung, and alveoli during a respiratory cycle?

How do we get air in and out of the alveoli?

InhaleExhale

Volumes that go through the mouth:• Tidal Volume• Vital Capacity

Volumes that exist inside the mouth• Residual Volume• End Expiratory Volume

(aka Functional Residual Capacity)• End Inspiratory Volume• Full Lung Capacity

The relationshipbetween thesevolumes and breathing

We can subdivide the space from the mouth inside:

Anatomically• Upper Airways • Lower Airways• Alveoli

Functionally• Alveolar (Gas Exchanging)• Physiologic Dead Space (Not)

} Anatomic Dead Space

Anatomic Dead Space Physiologic Dead Space

Flow:• Tidal Volume

through the mouth per breath• Total Ventilation

through the mouth per minute

• Alveolar Volumethrough the alveoli per breath

• Alveolar Ventilationthrough the alveoli per minute

We can use O2 and CO2 to Understand Volumes:

Fowler’s Method –Anatomic Dead Space

If you inhale a puregas, you will exhale:• Pure Gas• Mixed Gas• Alveolar Gas

Fowler’s Method –Anatomic Dead Space

Approximately 150 ccin a “regular man”

Bohr Equation – Physiologic Dead Space

All CO2 comes from alveolar gas (not dead space)

Arterial CO2 is almost always equal to Alveolar CO2

There is conservation of mass.

Bohr Equation – Physiologic Dead Space

PV = nRT

PACO2 * VA =number of molsof exhaled CO2

PECO2 * VT =number of molsof exhaled CO2

Bohr Equation – Physiologic Dead Space

So:

PACO2 * VA = PECO2 * VT =number of molsof exhaled CO2

Bohr Equation – Physiologic Dead Space

VA = PECO2 VT PACO2

VD = 1 - VA VT VT

VD = 1 - PECO2 VT PACO2

Bohr Equation – Physiologic Dead Space

V

V

P P

Pd

T

a E

a

CO CO

CO

2 2

2

Flow takes Work

We’ve already minimized workinvolved to move the chest and lung

Why waste work opening alveoli?

What is the “Residual Volume?”

The amount of air left in the lung after maximal exhale

It’s purpose: Keep the Alveoli Open

At low volumes, alveoli would collapse by:

• Absorbing the last air left behind

• Emptying to a larger alveoli(Surface Tension experiment)

Surfactants:

Are amphipathic molecules that forms a phospholipid monolayer lining the alveoli

The polar heads point at the alveolar wall, the lipophilic side chains point at the lumen

What is surfactant?• Mainly dipalmitoyl phosphatidylcholine

ProteinB

ProteinD

Surfactant

At low lung volumes:

In the small alveoli• The lipophilic tails of surfactant

are crowded and push each other away

• This keeps the alveoli open

At low lung volumes:

In the large alveoli• The viscosity of surfactant

resist overdistension

• This keeps the alveoli from expanding

Thus, surfactant acts to

1) keep airways and alveoli open during end expiration.

2) cause even distribution of air during late inspiration.

Surfactant resists LaPlace

Another mechanism exists to prevent alveolar collapse:

• Without cartilage – bronchiolestend to collapse

• During inhalation, lung expansionopens bronchioles

• During exhalation, bronchiolescan (and do) collapse

Another mechanism exists to prevent alveolar collapse:

• As the chest wall and lung recoil, the pressures in the lung increase

• These increased pressures start tostart to force bronchioles closed

• By the end of exhalation, almost allbronchioles are collapsed

Another mechanism exists to prevent alveolar collapse:

This is called:Small Airway Collapse

This gives lung a special property

The pressure-volume curve is different during inspiration and expiration.

This is known as Hysteresis

There are a variety of factors that influence the pressure-flow curve and cause hysteresis.

There are TWO main factors:• Surfactant• Collapse of Airways

Thus, surfactant causes the inspiratory portion of the hysteresis loop.

And collapse of airways causes the expiratory portion of the hysteresis loop

Just as total muscle force is afunction of average sarcomere length

Alveolar Compliance and functionis a function of average alveolar volume

These same mechanisms lead preferentially to isovolumetric alveoli

So is alveolar ventilation even across different regions of the lung?

No.

Findings:• Decreased flow to the upper lung• Increased flow to the lower lung

How do we explain regional differences in air flow to the lung?

Thus, net differences in ventilation are based on differences in intrapleural pressure.

These differences lead to different TRANSMURAL pressures, which lead to different flow rates.

Atmospheric Air has mostly nitrogen

Air that has been sitting in the nose, mouth, or trachea has water vapor

Air that has been in the alveoli has water vapor, CO2, and less O2

One of the challenges is Mixing:One of the challenges is Mixing:

Thus – Alveolar Ventilation is affected by:

• Total Flow in and out• Anatomic Dead Space• Functional Dead Space• Gas Mixing

To understand it you can:

1) Think about the gas compositionat each level (mouth, trachea, etc)

2) Think about the gas content as it travels “down” its pressure gradient

Atmospheric Pressure is 760 mmHg(at sea level)

Atmospheric Fraction of Oxygen is 21%

When Air goes through our upper airways, it becomes humidified and heated.

The partial pressure of water risesto 47 mmHg

PIO2 = (760 mmHg - 47 mmHg) * FIO2

PIO2 = Inspired O2 Partial PressureFIO2 = Fraction of Inspired O2

PIO2 = 713 * 21% = 150 mmHg

PAO2 = PIO2 – Pressure lost by displacement

PAO2 = Alveolar O2 Partial PressureThe effect of mixing!

Fortunately – CO2 Production is relatedto O2 Consumption

The body uses oxygen to harness energy from reduced carbon.

Depending on the carbon source (sugar, fat, protein) there are differing amounts of carbon dioxide produced

The Respiratory Quotient, R, is the number of moles of CO2 produced per mole of O2 consumed.

For a person eating a regular diet, it is approximately 0.8• It increases with fat metabolism• It decreases with sugar metabolism

PAO2 = PIO2 - PACO2 / R

R = Respiratory Quotient

PAO2 = 150 - PACO2 / 0.8

(just before mixing, arterial CO2 equals alveolar CO2)

PAO2 = 150 - PaCO2 / 0.8

PAO2 = (760 mmHg - 47 mmHg) * FIO2 - PartCO2 / 0.8

In a similar fashion, we can watch Carbon Dioxide

Pulmonary Artery brings in CO2 CO2 rapidly equilibrates with

alveolar CO2

During exhale alveolar gas mixeswith dead space gas displacing CO2

By end exhale, dead space gas is goneand CO2 is equivalent to alveolar CO2

Capnogram =measurement of exhaled pCO2

Already we’re seeing one of thedifferences between these gases:

Carbon Dioxide Equilibrates Quickly Oxygen Equilibrates Slowly

When we start to look more closely at oxygen, we discover:

The alveolar pO2 is higher than the arterial pO2

A-a gradient = PAO2 - PaO2

InMouth

Atmosphere

Thus, the things that reduce oxygen:• Barometric Pressure• Initial Inspired Fraction of Oxygen• Humidification (before and after)• Alveolar Mixing

• Diffusion Limits• Mixing with Deoxygenated Blood• Extraction by Tissue

The things that reduce carbon dioxide:

• Rate of Production of carbon dioxide• Total Buffer of carbon dioxide• Diffusion (not very limited)

• Alveolar Mixing• Dead Space Mixing

How does gas get from air to blood and back again?

It must cross the membrane which divides the alveoli and the capillary.

Is Described by Fick’s Law

(yes, you’ve seen it before)

Flow is proportional to Cross sectional area, Diffusion constant, Pressure gradient, The inverse of the thickness of the membrane.

Thus, to maximize gas flow:

1) the lung increases cross sectional area by extensive branching

2) the lung makes the membrane as thin as possible

3) the blood has mechanisms to increase rates of uptake or removal of gas

Each Gas (O2 , CO2 , CO, NO2 , N2O, Halothane) diffuses at a different rate.

Blood flows by at a (relatively) constant rate.

Thus, the total flow can be limited by either blood flow or diffusion.

As a result, in general:

• Gases are PERFUSION LIMITED in health

• But can become DIFFUSION LIMITED in disease.

Gas flows down its pressure gradient.

In general, the reservoir of gas will not be depleted.• There will always be O2 in the air (atmospheric and

both inhaled (21%) and exhaled (18%))• There will always be CO2 in the blood (arterial at

about 40 mmHg, venous at about 45 mmHg)

Furthermore, these pressures are relatively unchanged between pre and post exchange

The ability to maximize flow is the ability to make the recipient reservoir as empty as possible.

As a result• Oxygenation is based on PERFUSION• Carbon dioxide excretion is based on

VENTILATION.

When we use mechanical ventilation, we can only control ventilation.

Thus, we can affect blood carbon dioxide with ease.

Nevertheless, no changing in breathing will affect oxygenation

The ways we effect oxygenation by breathing is:

Increase the inspired oxygen• To increase the alveolar oxygen• Which will increase the diffusion gradient• Which will increase the flow of oxygen

Fix the underlying problem (perfusion)