Physiology II
Cardiovascular Physiology
Pulmonary Gas Exchange

readings REQUIRED or RECOMMENDED: Guyton and Hall (9^th edition). Chap. 39; Ganong (19^th edition), Chap. 34

Key Words

ideal gas law:  PV=nRT – The pressure of a gas is proportionate to its temperature and the number of moles per unit volume. Brody p.617

partial pressure:  the pressure exerted by any one gas in a mixture of gases (its partial pressure) is equal to the total pressure times the fraction of the total amount of gas it represents. The volume occupied by a given number of gas molecules at a given temperature and pressure is (ideally) the same regardless of the composition of the gas. The partial pressure of each gas in the alveolar respiratory gas mixture tends to force molecules of that gas into solution first, then in the blood of the alveolar capillaries. Brody 617

solubility coefficient:  one of the factors that determine the pressure of a gas dissolved in a fluid. Some types of molecules, especially CO2, are physically or chemically attracted to water molecules whereas others are repelled. When molecules are attracted, far more of them can then become dissolved without building up excess pressure within the solution. This relationship of solubility is described by the solubility coefficient. The complete list is on page 503 Guyton.

respiratory membrane:  membranes of all the terminal portions of the lungs, not merely the alveoli themselves. Note the following different layers: 1. A layer of fluid lining the alveolus and containing surfactant that reduces the surface tension of the alveolar fluid.

1. The alveolar epithelium composed of thin epithelial cells.
2. An epithelial basement membrane.
3. A thin interstitial space between the alveolar epithelium and the capillary membrane.
4. A capillary basement membrane that in many places fuses witht the epithelial basement membrane.
5. The capillary endothelial membrane.

pulmonary diffusion capacity (D_L):  the volume of a gas that diffuses through the membrane each minute for a pressure difference of 1mmHg. This describes the ability of the respiratory membrane to exchange a gas between the alveoli and the pulmonary blood.

diffusion rate:  the factors that determine how rapidly a gas will pass through the membrane are: 

1. thickness of the membrane
2. surface area of the membrane
3. diffusion coefficient of the gas in the substance of the membrane
4. the pressure difference between the two sides of the membrane

fractional concentration (F):  

ambient air:  atmospheric air

inspired air:  the volume of external air that is taken in with each breath and humidified

alveolar air:  the volume of humidified air that exists in the alveoli

expired air:  the volume of air that is breathed out with each breath, and is a combination of dead space air and alveolar air

alveolar gas partial pressures:  the pressure exerted by any one gas in the mixture of gases that exists in the alveoli at any one point in time

ventilation-perfusion ratio (V_A/Q):  Va/Q – the ratio of pulmonary ventilation to pulmonary blood flow for the whole lung at rest. In a healthy human subject, is about 0.8 (4.2L/min ventilation divided by 5.5L/min blood flow)

regional differences in ventilation-perfusion ratios:  in various parts of the normal lung, there are relatively marked differences in this ratio as a result of the effect of gravity, and local changes are common in disease. In the upright position, ventilation as well as perfusion declines in a linear fashion from the bases to the apices of the lungs. In the upper portions there is relatively more ventilation than perfusion, and in the bases relatively more blood flow than ventilation.

A-a 0₂ difference:  refers to the pressure gradient that exists between the Alveolar oxygen level and the arterial oxygen level at the aorta

Learning Objectives:

describe the basic physical principles of gases, including the various laws describing the relationships among pressure, volume, and temperature:  Unlike liquids, gases expand to fill the volume available to them, and the volume occupied by a given number of gas molecules at a given temperature and pressure is (ideally) the same regardless of the composition of the gas. Gases diffuse form areas of high pressure to areas of low pressure, the rate of diffusion depends on the concentration gradient and the nature of the barrier between the two areas. The partial pressures at sea level of the gases in the air reaching the lungs are PO2 – 149mmHg, PCO2 – 0.3mmHg, and PN2 – 564mmHg. These relationships are described by a number of individual laws, but are combined into the Ideal Gas Law as described above.

understand the standard notations used in Respiratory Physiology for quantities (pressure, fractional concentration, content, etc.), locations (arterial, alveolar, inspired, etc.), and rates (minute ventilation, alveolar ventilation, etc.):  

• Pressure – a force caused by the constant impact of kinetically moving molecules against a surface
• Content – the primary component of oxygen content is the amount of oxyhemoglobin in the blood
• Minute ventilation – the total amount of new air moved into the respiratory passages each minute. On average about 6L/min
• Alveolar ventilation – the amount of air reaching the alveoli per minute
• Anatomic dead space – the respiratory anatomy that does not participate in gas exchange
• Physiologic dead space – volume of gas not equilibrating with blood (wasted ventilation)
• Tidal volume – the amount of air that moves into the lungs with each inspiration
• Inspiratory reserve volume – the air inspired with a maximal inspiratory effort in excess of the tidal volume
• Vital capacity – the largest amount of air that can be expired after a maximal inspiratory effort

discuss the concept of partial pressure as it applies to gas mixtures (e.g., alveolar air) and gasses dissolved in aqueous solutions (e.g., pulmonary capillary blood) and the movement of oxygen and carbon dioxide between these two regions:  Gases dissolved in water or body tissues exert pressure because the dissolved molecules are moving randomly and have kinetic energy. When the molecules of a gas dissolved in fluid encounter a surface like the membrane of a cell, they exert their own pressure in the same way that a gas in the gas phase exerts its own individual pressure. This pressure is determined by the concentration and the solubility coefficient of the gas. Some gases dissolve better than others, and if there is more of it, it will dissolve quicker! The gases that are of respiratory importance are all highly soluble in lipids and therefore cell membranes. The major limitation is the water they must pass to get to the right place. Diffusion of gases through tissues is almost equal to the diffusion of gases through water.

The PO2 of alveolar air is normally 100mmHg, and of the blood entering the pulmonary capillaries is 40mmHg. The diffusing capacity for O2 is about 25mL/min/mmHg. The O2 diffuses across the alveolar membrane into the pulm. Capillary according to this gradient, and the blood PO2 is raised to 97% as it passes the alveoli, but is reduced to about 95% in the aorta due to physiologic shunt.

The PCO2 of mixed venous blood is 46mmHg, whereas the alveolar PCO2 is 40mmHG, and CO2 diffuses from the blood into the alveoli along this gradient. The PCO2 of blood leaving the lungs is 40mmHg. CO2 passes through all biological membranes with ease, and the diffusing capacity of the lung for CO2 is much greater than the capacity for O2.

name and describe the components of the respiratory membrane and their functional significance:  (see key words)

define the term "pulmonary diffusion capacity (D_L) ", describe its determination using the gas carbon monoxide (D_Lco), and its significance in pulmonary gas exchange:  Pulmonary diffusion capacity – (DL) - is defined as the volume of a gas that diffuses through the membrane each minute for a pressure difference of 1mmHg, and describes the ability of the respiratory membrane to exchange a gas between the alveoli and the pulmonary blood. The O2 diffusing capacity is calculated from measurements of A) alveolar PO2,

B) PO2 in the pulmonary capillary blood, and C) the rate of O2 uptake by the blood. Because measuring O2 was difficult, scientists use CO instead, then calculate the O2 from this. To convert the CO diffusing capacity to O2, the value is multiplied by a factor of 1.23 which is the diffusion coefficient for O2. The average diffusing capacity for O2 is calculated at 21ml/min/mmHg.

using Fick's Law of Diffusion as a framework, identify the physical factors that influence the rate of diffusion of gases across the respiratory membrane:  Some basic tenets of diffusion include:

1. Gases diffuse from areas of high pressure to areas of lower pressure
2. The main determinant of diffusion of any gas, with all other factors being equal, is concentration gradient.
3. Heat increases the molecular movement of gases and the rate of diffusion.
4. Gases differ in their solubility coefficients as well as other physical properties, and therefore, diffuse at different rates.
5. The thickness of the membrane as well as the surface area also contribute to the determination of rate of diffusion

Fick’s law of diffusion states that the rate of diffusion of a gas in an inhomogeneous mixture is proportional to the concentration gradient.

Graham’s law states that the rate of diffusion of a gas is inversely proportional to the square root of the molecular weight, the heavier the molecule, the slower the diffusion.

describe qualitatively the effects of each of the following on D_Lco: anemia, polycythemia, blood loss, Valsalva maneuver; moving from a supine to a standing position; exercise; pneumonectomy; pulmonary edema; pulmonary fibrosis; emphysema; smoking:  The effects of the following conditions on the pulmonary diffusion capacity are:

1. supine to upright position (less blood volume in chest)– diffusion capacity down
2. fibrosis (membrane thick) – down
3. valsalva ( less bv in chest)– down
4. anemia (less Hgb)– down
5. pneumonectomy (less surface area) – down
6. blood loss (less bv) – down
7. exercise (more blood volume)– up
8. pulmonary edema (less sa, more thickness)– down
9. emphysema (less sa)– down
10. polycythemia (more viscous more Hgb)– up
11. smoking (less sa, more thickness)- down

state the typical fractional concentrations and partial pressures of oxygen and carbon dioxide in ambient air, inspired air, alveolar air, and expired air, and state typical values for partial pressures of oxygen and carbon dioxide in mixed venous blood and arterial blood:  typical fractional concentrations and partial pressures of O2 + CO2 in

• ambient air –O2 – 159, CO2 – 0.3
• inspired air – O2 – 149.3, CO2 – 0.3
• alveolar air – O2 – 104, CO2 - 40
• expired air – O2 – 116, CO2 – 32
• PPO2 mixed venous blood – 40
• PPO2 arterial blood –95
• PPCO2 mixed venous blood – 46
• PPCO2 arterial blood –40

describe using words or a diagram the approximate magnitude and significance of regional differences in ventilation-perfusion ratios that exist in the lung of a healthy, normal human subject standing upright/demonstrate an understanding of the concept of venous admixture or shunting and its effect of arterial partial pressures of oxygen and carbon dioxide:  In a normal person in the upright position, both blood flow and alveolar ventilation are considerably less in the upper portion of the lung than in the lower part; but blood flow is decreased considerably more than is ventilation. At the top of the lung Va/Q is as much as 2.5 times as great as the ideal value, which causes a moderate degree of physiologic dead space.

At the other extreme, at the bottom of the lung, there is slightly too little ventilation in relation to blood flow, with Va/Q as low as 0.6 times the ideal value. In this area, a small fraction of blood fails to become oxygenated and this represents physiologic shunt.

The ideal Va/Q is 0.8 at rest. (this represents 4.2L/min ventilation divided by 5.5L/min blood flow)

In every normal human subject, there exists a small physiologic shunt created by anastomoses between the bronchial capillaries and the pulmonary capillaries and veins, which some blood enters - bypassing the right ventricle. The other, is blood that flows from the coronary arteries into the chambers of the left side of the heart, also bypassing the lungs. These enter the aorta as unoxygenated blood therefore reducing the PO2 by about 2mmHg and this reduces the SaO2 by 2-5% making the saturation about 95-98%.

list and discuss the causes of the alveolar-arterial PO₂ difference (A-a 0₂ difference) in a healthy human subject:  A – a O2 difference in a normal healthy human subject is related to the physiologic shunts that exist in #10, and describes the concentration gradient for which diffusion will occur.

calculate the A-a 0₂ difference, using the alveolar air equation and values for inspired P0₂, respiratory exchange ratio, and arterial or alveolar PC0₂ provided in a patient case study:  PAO2=PIO2-PACO2/R(.8) I calculated using the numbers given to us in respiratory case D. barometric pressure is 446

• PAO2=(446*.21)-27/.8
• PAO2=93.7-27/.8
• PAO2=83.4 which is approximately the PO2 provided in the example (84)

Last Updated 09/06/01 08:53:26 PM
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