RESPIRATORY SYSTEM (PART 2) - mechanics of respiration part 2 -

- diffusion of gases -

Formas de la respiration , 1961; painting by Jorge de la Vega (Argentine)

Dr Denise Zahiu

Clinical case• Male, 20-years-old, never smoked

• Since childhood he had attacks of wheezing and shortness of breath precipitated by high pollen levels and cold weather.

Spirometry Predicted mean and the lower limit of normal

Pre-BD Post-BD

FEV1 (L) 4.3 (3.58) 2.25 3.20

FVC (L) 5.10 (4.25) 4.25 4.40

FEV1/FVC (%) 83 (74) 53 73

FEF 25-75% (L/s) 4.7 (3.2) 2.1 3.9

PEF (L/s) 9.4 (7.3) 5.5 8.3

1. What is the diagnosis of this patient?

• The concavity in the expiratory flow-volume curve and the low Tiffneau index indicates an obstructive ventilator defect.

• Pre-bronchodilator FEV1/FVC ratio is 53% and FEV1 is 52% predicted indicating a moderately severe obstructive ventilator defect.

• There was a 42% (0.95 L) improvement in FEV1 post-bronchodilator indicating substantial reversibility.

Evolution of the patient• Treatment with an inhaled bronchodilator (beta 2 adrenergic agonist)

was started to treat the attacks.

• …after 23 years: His asthma attacks were becoming more severe and more frequent and he has been taken to the emergency room five time in the past year.

• Now he presents to the emergency room with fever, nasal and chest congestion, exhausted from “just trying to breathe”. He had inspiratory and expiratory wheezes and was in severe respiratory distress. Respiratory rate 30 breaths/min (normal 12-15)

pH 7.48 (normal 7.4)

PaO2 55 mmHg (normal 100mmHg)

Pa CO2 32 mmHg (normal 40 mmHg)

Measurements done at room air (21%O2 concentration)

2.What is the actual problem of the patient?• An upper respiratory infection that precipitated a severe asthma attack

with respiratory failure as shown by blood gases (low PaO2).

3.Asthma is an obstructive disease in which the airways narrow (medium and small airways), increasing the resistance to airflow into and out of the lungs. What are the relationships between airflow, resistance and airway diameter?• Asthma is characterized by inflammation of the airways. This leads to: swelling of airways mucosaincreased production of mucuscontraction of airway smooth muscle (bronchospasm)

Increase airways resistance

Air flow is proportional to the difference between alveolar and atmospheric pressure, but inversely proportional to AIRWAYS RESISTANCE.

R ~ 8 L/r4

R = airways resistance to air flow L = length of the system ~ constant = viscosity of inspired air ~

constant in normal conditions r = radius of the airways is the

primary determinant of R

neuro-hormones lung volume (VL) flow of air through the airway

Neuro-hormones:a. The vagus nerve – release acetylcholine – bronchoconstriction through

muscarinic receptors; atropine, an antagonist, block this effectb. The sympathetic system (of autonomous nervous system) –release

norepinephrine (NE) via β2-adrenergic receptors – bronchodilation and reduces mucus secretion. Other β2-agonists –albuterol, epinephrine (more potent than NE)

c. Histamine, slow reactive substance of anaphylaxis, leukotrienes, cytokines– are released during allergic reactions and induce bronchoconstriction

Airways diameter is an important factor that influence airways resistance (r4) and it is influenced by:

LUNG VOLUME influence on airways resistance

LUNG VOLUME influence on

airways resistance

Flow of air can dilate or collapse the airways to the extent that their compliance permits

Equal pressure point

During effort….the maximum expiratory air flow decreases as the lung volume becomes smaller and the equal pressure point moves toward the more collapsible peripheral airways

Dependence of airflow on effort. In D, note that if airway resistance were fixed, increased effort (i.e., increased PA) would yield a proportionate increase in ΔV , as indicated by the red line. However, increased effort tends to narrow airways, raising resistance and tending to flatten the curves. As VL decreases (e.g., 4 or 3 L), airflow becomes independent of effort with increasingly low effort. PB, PIP, PTP, and PA are all in centimeters of H2O.

Air flow patterns influnces the resistance to air flow

Types of air fow: laminar, transitional, and turbulent flow.

In A, laminar airflow (ΔV ) is proportional to the driving pressure (ΔP = P1 − P2).

In C, where turbulent airflow is proportional to the square root of the driving pressure, a greater ΔP (i.e., effort) is needed to produce the same ΔV as in A. This air flow pattern has the highest resistance to air flow.

Trachea and bronchi determine 90% of airways resistance because

they are rigid structures, supported by cartilage with a radius ~ constant

mucus accumulation increase R even more

Bronchioles - 10% of airways resistancetotal cross-sectional area = 2000 times that of trachea

nonrigid, they can collapse broncho-dilation/constriction

4. What effect did asthma attack have on residual volume and functional residual capacity?

Asthma is associated with increased airway resistance which compromised the expiratory function. The equal pressure point moves to collapsible peripheral airways and closes prematurely the small airways. As a result the air that should have been expired remained in the lungs (air trapping), increasing the residual volume and FRC.

5.Why was the patient exhausted from “just trying to breathe? How does obstructive lung disease increase the work of breathing?

The work of breathing is determined by how much pressure change is required to move air into and out of the lungs. In asthma, the work of breathing is increased for 2 reasons:1. A person with asthma breathes at higher lung volumes (higher

FRC). During inspiration the patient must lower intrathoracic pressure more than a healthy person.

2. During expiration, because airway resistance is increased, higher pressure must be created to force air out of the lungs. This greater expiratory effort requires the use of accessory muscles.

Respiratory rate 30 breaths/min (normal 12-15)

pH 7.48 (normal 7.4)

PaO2 55 mmHg (normal 100mmHg)

Pa CO2 32 mmHg (normal 40 mmHg)

Measurements done at room air (21%O2 concentration)

5. Why was the patient’s arterial PaO2 decreased? How does the pulmonary gas exchange is done?

Diffusion of Respiratory Gases

Partial Pressures of Respiratory Gases

• The pressure of a mixture of gases is equal to the sum of the pressures of all of the constituent gases alone:

PressureTotal = Pressure1 + Pressure2 ... Pressuren

• Each gas contributes to the total pressure of a mixture of gases in direct proportion to its concentration:

Partial pressure = Total pressure x Gas concentration

Atmospheric air

(mm Hg)

Humidified air

(mm Hg)

Alveolar air

(mm Hg)

Expiratory air

(mm Hg)

N 2

O 2

CO 2

H 2O

TOTAL

597.0 (78.62%)

159.0 (20.84%)

0.3 ( 0.04%)

3.7 (0.50%)

760.0 (100%)

563.4 (74.09%)

149.3 (19.67%)

0.3 (0.04%)

47.0 (6.20%)

760.0 (100%)

569.0 (74.9%)

104.0 (13.6%)

40.0 (5.3%)

47.0 (6.2%)

760.0 (100%)

566.0 (74.5%)

120.0 (15.7%)

27.0 (3.6%)

47.0 (6.2%)

760.0 (100%)

Slow replacement of alveolar air gas composition in the alveoli varies slightly during normal breathing prevent sudden changes in gas concentrations and the pH of the blood

350 mL fresh air/breath reaches alveoli ~ 1/7 of total lung volume at the end of a quiet inspiration

Alveolar Air Composition• Is different from the composition of the atmospheric air because:

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

• oxygen is constantly being absorbed into the pulmonary blood from the alveolar air

• carbon dioxide is constantly diffusing from the pulmonary blood into the alveoli

• atmospheric air that enters the respiratory passages is humidified even before it reaches the alveoli

Oxygen and carbon dioxide partial pressures in the expired air

• Oxygen concentration in the alveoli is controlled by

– the rate of absorption of oxygen into the blood

– the rate of entry of new oxygen into the lungs by the ventilatoryprocess

• The alveolar PCO2

– increases directly in proportion to the rate of carbon dioxide excretion

– decreases in inverse proportion to alveolar ventilation

Respiratory Membrane

1. Alveolar fluid with surfactant

2. Alveolar epithelium

3. Epithelial basement membrane

4. Thin interstitial space between the alveolar epithelium and the capillary membrane

5. Capillary basement membrane

6. Capillary endothelial cells

Has: 0.6 mm thickness70 square meters

Pulmonary capillary diameter: 5 mmBlood volume in pulmonary capillaries: 60 - 140 ml

Diffusion of gases

Gas Diffusion Trough the Respiratory Membrane

Depends on:

1. The thickness of the membrane

• increased in pulmonary edema, fibrosis

2. The surface area of the exchange membrane

• decreased in emphysema

• increased during exercise when more capillaries are open

3. The diffusion coefficient of the gas in the substance of the membrane

4. The partial pressure difference of the gas between the two sides of the membrane

5. The temperature

• fairly constant in the body, therefore negligible

Diffusion Rate

D = diffusion rate of the gas

ΔP = pressure gradient across the membrane

A = cross-sectional area

S = solubility coefficient of the gas

d = distance of diffusion

MW = molecular weight of the gas

The characteristics of the gas itself, S and MW, determine the diffusion coefficient of the gas ~ S/ MW

ΔP x A x S

d x MWD ~

Diffusion Rate

Solubility Coefficient of a Gas• The partial pressure of a gas in a solution is determined not only

by its concentration but also by the solubility coefficient of the gas

• Henry’s law:

Partial pressure = Concentration of dissolved gas/ Solubility coefficient

• Solubility coefficient (S) of a gas depends on the physical or chemical attraction to water molecules; a higher attraction means a better solubility and a lower partial pressure developed for a given concentration

How can be evaluated the diffusion capacity of the respiratory membrane?

DLCO = TLCO = the diffusing capacity or transfer factor of the lung for carbon monoxide (CO). This test involves measuring the partial pressure difference between inspired and expired CO. It relies on the strong affinity and large absorption capacity of red blood cells for CO and thus demonstrates gas uptake by the capillaries.

DLCO is an index of the surface area available for gas exchange and is decreased in emphysema, alveolar inflammation, and pulmonary fibrosis.

Single Breath Technique is the most common way to determine DLCO

• The test is performed by having the subject blow out all of the air that they can, leaving only the residual lung volume of gas. The person then inhales a test gas mixture rapidly and completely, reaching the total lung capacity as nearly as possible.

• This test gas mixture contains a small amount of carbon monoxide (usually 0.3%) and a tracer gas that is freely distributed throughout the alveolar space but which doesn't cross the alveolar-capillary membrane. Helium and methane are two such gasses.

• The test gas is held in the lung for about 10 seconds during which time the CO (but not the tracer gas) continuously moves from the alveoli into the blood. Then the subject exhales.

Single Breath Technique is the most common way to determine DLCO

• The rate at which CO is taken up by the lung is calculated knowing the variation in CO concentration during the breath hold.

• The volume of the alveoli, VA, is determined by the degree to which the tracer gas has been diluted by inhaling it into the lung.

• The alveolar carbon monoxide fraction (FACO) is the fractional concentration of carbon monoxide in the alveolar space.

• Thus, at a constant volume, the transfer of carbon monoxide from the lungs into the blood is VA·ΔFACO/Δt.

• PACO = partial pressure of alveolar CO

Other methods that are not so widely used at present can measure the DLCO. These include the steady state diffusing capacity that is performed during regular tidal breathing.

Factors that Affect DLCO (TLCO)

DLCO in asthma

• The DLCO in patients with asthma is either within normal limits or high depending on several factors. In asthmatic patients with preserved lung function, the DLCO is typically normal.

• In moderate to severe asthma the DLCO is usually elevated and will also increase with bronchodilator treatment. The high DLCO values have been explained by hyperinflation, increased intrathoracic pressure, and a more likely cause, increases in pulmonary capillary blood volume or extravasation of red blood cells into the alveolus.

(Pulmonary Physiology in Asthma and COPD, Charles G. Irvin,2009)

O2 Diffusion

Diffusion capacity for O2

Oxygen transport in blood

O2 from alveoli diffuse into the blood through the respiratory membrane.

O2 enters the RBC and binds to hemoglobin (Hb)

3% of O2 is dissolved in plasma 97% is bound to Hb

The binding is reversible Hb + O2 OxyHb

CO2 Diffusion

CO2 transport in blood

Tissue -blood

In blood:

10% Dissolved CO221%carbaminohemoglobin69% HCO3-

Tissue Lungs

Answer question 5: Our patient has hypoxia (normal PaO2 is 98-100mmHg)

Which are the causes for hypoxia?

Examples of pulmonary pathologies that lead to hypoxia

Asthma:

Decreased airway ventilation secondary to increased airway resistance induces changes in alveolar air composition. The O2 pressure in alveolar air is decreased and CO2 pressure is increased.

Is a ventilation - perfusion mismatch.Bronchoconstriction and obstruction (with mucus) of some airways prevented adequate ventilation of some regions of the lungs. Therefore, the pulmonary capillary blood that perfused these unventilated alveoli was not oxygenated.

6. What acid-base abnormality did the patient have and why?

Respiratory rate 30 breaths/min (normal 12-15)

pH 7.48 (normal 7.4)

PaO2 55 mmHg (normal 100mmHg)

Pa CO2 32 mmHg (normal 40 mmHg)

Measurements done at room air (21%O2 concentration)

He had respiratory alkalosis secondary to hyperventilation.

Why did he hyperventilates?He was hyperventilating secondary to hypoxemia. Detailed answer in the next lecture (regulation of ventilation)

Methods for the evaluation of anatomic dead space

Methods for the evaluation of anatomic dead space