3 important gas laws govern ambient air and alveolar ventilation:

1. Boyle’s law2. Dalton’s law3. Henry’s law

Dalton’s Law of Partial Pressures

states that the total pressure exerted by a mixture of gases is the sum of the pressures exerted independently by each gas in the mixture.

Further, the pressure exerted by each gas—its partial pressure—is directly proportional to the percentage of that gas in the gas mixture.

Barometric pressure (PB) – 760 mmHg

O2 – 21%

Po2 = 160 mm Hg

N2 – 79%

PN2 = 600 mm Hg

Dalton’s Law of Partial Pressures

HENRY’S LAW when a mixture of gases is in

contact with a liquid, each gas will dissolve in the liquid in proportion to its partial pressure

Thus the greater the concentration of a particular gas in the gas phase, the more and the faster that gas will go into solution in the liquid.

The amount of gas that will dissolve in a liquid also depends upon its solubility

Various gases in air have different solubilities: Carbon dioxide is the most soluble Oxygen is 1/20th as soluble as carbon

dioxide Nitrogen is practically insoluble in

plasma

Henry’s Law

FICK’S LAW OF DIFFUSION

The net diffusion rate of a gas across a fluid membrane is proportional to the difference in partial pressure proportional to diffusion coefficient ( molecular

weight and solubility of gas) proportional to the area of the membrane and inversely proportional to the thickness of the

membrane

Diffusion rate

Surface area x conc. gradient x membr. permeability

Membrane thickness

Transfer of gases occurs by simple diffusion

GAS EXCHANGE

• refers to DIFFUSION of O2 and CO2 in the lungs and in the peripheral tissues

The driving force for gas exchange is the partial pressure difference of the gas (ΔP) across the

membrane, NOT the concentration

difference.

Partial Pressure Gradients:

O2 flows “downhill”

Alveoli Blood Tissues

CO2 flows “downhill”

Alveoli Blood Tissues

RESPIRATORY MEMBRANE

Respiratory Membrane

only 0.6 m thick, allowing for efficient gas exchange

Have a total surface area (in males) of about 70 m2 (40 times that of one’s skin)

RESPIRATORY MEMBRANE

Diffusion of gases through the respiratory membrane depends upon:

1. Membrane thickness in fibrosis or pulmonary edema, diffusion

↓s

2. Diffusion coefficient of gas affected by solubility and molecular weight

CO2 more soluble in water than O2 Oxygen more soluble than nitrogen Equal amounts of carbon dioxide and

oxygen are exchanged

Diffusion of gases through therespiratory membrane depends upon:

3. Surface area Diseases like emphysema , lung

cancer, TB reduce available surface area

During exercise, additional capillaries are perfused with blood, which increases the surface area for exchange

Diffusion of gases through the respiratory membrane depends upon:

3. Surface area

When the total surface area is decreased to 1/3 -1/4 normal, it becomes significant

Highpressure

Lowpressure

Diffusion of gases through the respiratory membrane depends upon:

4. Partial pressure differences Gas moves from area of higher partial

pressure to area of lower partial pressure. Normally, partial pressure of oxygen is higher in alveoli than in blood. Opposite is usually true for carbon dioxide

Differences in partial pressure Small diffusion distance Lipid-soluble gases Large surface area of all alveoli

Gas exchange across respiratory membrane is efficient due to:

LUNG DIFFUSING CAPACITY (DL)

Combines :the diffusion coefficient of the gasthe surface area of the membrane

the thickness of the membrane

LUNG DIFFUSING CAPACITY (DL)

In emphysema, DL decreases because of destruction of alveoli resulting to decreased surface area

In fibrosis or pulmonary edema, DL decreases because membrane thickness increases

In anemia, DL decreases During exercise, DL increases

GAS EXCHANGE ACROSS PULMONARY CAPILLARIES

• Both oxygen and carbon dioxide diffuse down their concentration (partial pressure) gradients

LUNG PO2 = 100mmHgPCO2 = 40mmHg

PO2 = 40mmHgPCO2 = 46mmHg

PULMONARY CAPILLARIESPO2 = 100mmHgPCO2 = 40mmHg

GAS EXCHANGE ACROSS SYSTEMIC CAPILLARIES

• Both oxygen and carbon dioxide diffuse down their concentration (partial pressure) gradients

TISSUE PO2 < 40mmHgPCO2 > 46mmHg

PO2 = 40mmHgPCO2 = 46mmHg

SYSTEMIC CAPILLARIESPO2 = 100mmHgPCO2 = 40mmHg

VENTILATION, PERFUSION AND V/Q RELATIONSHIPS

VENTILATION and PERFUSION are important components of gas exchange in the lung

However, the major determinant of gas exchange and thus the level of PO2 and PCO2 in the blood is the relationship between ventilation and perfusion

VENTILATION

Process by which air moves in and out of the lung MINUTE VENTILATION ALVEOLAR VENTILATION

Minute and Alveolar Ventilation

Minute ventilation: total amount of air entering

or leaving the lungs each minute

Alveolar ventilation:volume of air that enters the alveoli each minute

MINUTE VENTILATION respiratory minute volume; pulmonary ventilation

VE =500 ml/breath X 12 breaths/min

Normally about 6 liters

VE = VT • f

ALVEOLAR VENTILATION

VA = (500 ml/breath -150 ml) X 12 breaths/min

Normally about 4.2 liters

VA = (VT-VD) • f

Alveolar Ventilation

Slow, deep breathing increases AVR

rapid, shallow breathing decreases AVR

VA = (VT-VD) • f

AMBIENT AIR

Gas mixture composed of N2 and O2 with minute quantities of CO2. argon and inert gases

As we inspire the air, it is warmed to body temperature and humidified

INSPIRED AIR

becomes saturated with water vapor, which exerts a partial pressure and dilutes the total pressure of the other gases

Water vapor pressure at body temperature is 47mmHg

GAS Atmospheric air(mmHg)

Humidified air

(mmHg)

N2 597 563

O2 159 149

CO2 0.3 0.3

H2O 3.7 47

ALVEOLAR GAS: composition

contain more CO2 and water vapor and much less O2

These differences reflect the effects of:

1. gas exchanges occurring in the lungs (O2 diffuses from the alveoli into the pulmonary blood and CO2 diffuses in the opposite direction)2. humidification of air by conducting passages3. the mixing of alveolar gas that occurs with each breath

GAS Atmospheric air

(mmHg)

Humidified air

(mmHg)

Alveolar air

(mmHg)

N2 597 563 569

O2 159 149 104

CO2 0.3 0.3 40

H2O 3.7 47 47

alveolar air is only partially replaced by atmospheric air with each breath

Because only 500 ml of air is inspired with each tidal inspiration, gas in the alveoli is actually a mixture of newly inspired gases and gases remaining in the respiratory passageways between breaths.   

Rate at which alveolar air is renewed by atmospheric air:

FRC measures 2300ml BUT only 350ml of new air is brought into the alveoli with each normal respiration

Amount of alveolar air replaced by new atmospheric air with each breath is only 1/7

At normal alveolar ventilation , approximately half of the gas is exchanged in 17 seconds

What controls alveolar ventilation?

PaCO2 in arterial blood that regulates ventilation

↑ PaCO2 ventilation rises

↓ PaCO2 ventilation falls

DEAD SPACE VENTILATION

Ventilation to airways that do not participate in gas exchange

2 types of dead space:1. anatomic dead space2. physiologic dead space

ANATOMIC DEAD SPACE

composed of the volume of gas that fills the conducting airways

In a healthy individual, 30% of the inspired air is wasted

PHYSIOLOGICAL DEAD SPACE VENTILATION

The total volume of gas in each breath that does not participate in gas exchange

Includes the anatomic dead space and the dead space secondary to the ventilated but not perfused alveoli

nearly equal in normal

PERFUSION

Process by which deoxygenated blood passes through the lung and becomes oxygenated

PULMONARY CIRCULATION

Begins with the right atrium Total blood volume: 500ml Low pressure, low resistance

system

Regulation of Pulmonary blood flow

Hypoxic vasoconstriction Mechanism: direct action of alveolar

PO2 on the vascular smooth muscle of pulmonary arterioles

HYPOXIC VASOCONSTRICTION

Hypoxia causes depolarization of vascular smooth muscle cells → depolarization opens voltage-gated calcium channels → calcium influx → contraction

VENTILATION-PERFUSION RELATIONSHIPS

Ratio of ventilation to blood flow Ventilation and perfusion must be

tightly regulated for efficient gas exchange

VENTILATION-PERFUSION COUPLING (V/Q ratio)

Ratio of pulmonary ventilation to pulmonary blood flow

Ratio of CO2 excreted to the O2 taken up by the lungs

= CO2 consumption

O2 consumption

Respiratory exchange ratio Normally, 0.8

DIFFERENCES IN VENTILATION & PERFUSION IN DIFFERENT PARTS OF

THE LUNG

UPRIGHT POSITION Ventilation is greater at

the base Perfusion is greater at

the base

LATERAL POSITION The dependent lung is

best ventilated

Ventilation/Perfusion Ratios

In an upright subject, ventilation increases more slowly than blood flow from the apex of the lung to the base

Insert fig. 16.24

The difference in V/Q ratios is associated with a difference in alveolar O2 and CO2 content between apex and the base

APEX : high alveolar O2, low alveolar CO2

BASE : low alveolar O2, high alveolar CO2

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Alveolar-arterial PO2 difference

Difference between alveolar O2 (PAO2) and arterial PO2 ( PaO2)

Normally, alveolar O2 (PAO2) is slightly greater than arterial PO2

( PaO2)

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If PAO2 normally averages 100 mmHg,

why is average PaO2 =95 mmHg??

1. Shunt

- small fraction of pulmonary blood flow bypasses the alveoli

2. V/Q differences from apex to base

SHUNT 2 sources:

1. some bronchial and mediastinal veins drain into the pulmonary veins

2. Small portion of coronary venous blood (thebesian vessels) that drains directly into the left ventricle rather than going to the lungs to be oxygenated

SHUNT (VENOUS ADMIXTURE)

Normally 1-2% of total cardiac output

Alveolar-arterial PO2 difference

An increased in AaDO2 is a hallmark of abnormal O2 exchange

In normal individuals breathing room air, AaDO2 is less than 15mmHg

The A-a Gradient

The A-a gradient = PAO2 – PaO2

Normal A-a gradient ≈ (age + 10) / 4 Can range between 5-20 mmHg

The A-a Gradient

useful in determining source of hypoxemia

INCREASES with age For every decade a person lived,

gradient is expected to increase by

1 mmHg

The A-a Gradient

If abnormally INCREASED, denotes poor gas exchange

Seen in : Defect in diffusion V/Q defect R to L shunt

V/Q DEFECTS

Ventilation/perfusion defects:

VA/Q = 0• •

PAO2 = 40PACO2 = 45

PvO2 = 40PvCO2 = 46

Pc'O2 = 40Pc'CO2 = 46

PO2 = 150PCO2 = 0

• Without alveolar ventilation, VA/Q = 0

pO2 in the alveolus falls

Alveolar PO2 will decrease to 40

mmHg pCO2 rises

Alveolar PCO2 will increase to 45

mmHg

•This is “shunt”

V/Q ratio=0

Shunts: when perfusion exceeds ventilation, a shunt exists. Blood bypasses the alveoli w/o gas exchange occurring.

Airway obstruction, mucous plugs, right to left cardiac shunts

V/Q ratio=0

Results in an increase in “physiologic shunt blood”- blood that is not oxygenated as it passes the lung

PAO2 = 150PACO2 = 0

PO2 = 150PCO2 = 0

VA/Q = ∞• •

Ventilation/perfusion defects: Dead space

• Without perfusion, VA/Q = ∞

• Ventilation exceeds perfusion

• Alveoli do not have adequate blood supply for gas exchange to occur

• •

PAO2 = 150PACO2 = 0

PO2 = 150PCO2 = 0

VA/Q = ∞• •

Ventilation/perfusion defects: ↑ V/Q ratio

• Alveolar gas tensions would equal those in inspired air

• This is “dead space” or wasted

Pulmonary emboli, pulmonary infarction, cardiogenic shock

• •

HIGH V/Q

High ventilation relative to perfusion usually because blood flow is decreased

Unlike dead space, which has no perfusion, high V/Q regions have some blood flow

Pulmonary capillary blood has a high PO2 and a low PCO2

LOW V/Q

Regions have low ventilation relative to perfusion

Pulmonary capillary blood has a low PO2 and a high PCO2

IN SUMMARY ……

the gas exchanges that occur between the blood and the alveoli and between the blood and the tissue cells take place by simple diffusion driven by the partial pressure gradients of O2 and CO2 that exist on the opposite sides of the exchange membranes.

Pulmonary blood flow and ventilation – unevenly distributed

Apex – blood flow is lowest as well as ventilation

V/Q highest at the apex, with an average value of 0.8

Where V/Q is highest, PaO2 is highest and PaCO2 is lowest

V/Q defects impair gas exchange If ventilation is decreased relative to

perfusion, then PAO2 and PACO2 will approach their values in mixed venous blood

If perfusion is decreased relative to ventilation, then PAO2 and PACO2

will approach their values in inspired air

QUESTIONS?

Thank you