Principles of Gas Exchange and Transport Summary

Expired Air Composition

Expired air is a combination of dead space air and alveolar air.
The overall composition is determined by:
- Dead space air (humidified).
- Progressively more alveolar air mixing in.
- At the end of expiration, only alveolar air is expelled.
Alveolar air is collected from the last portion of expired air after forceful expiration.

Principles of Gas Exchange: Diffusion of Oxygen and Carbon Dioxide

Partial pressures of oxygen ( $Po2$ ) and carbon dioxide ( $Pco2$ ) are key factors.

Respiratory Unit

The respiratory unit (or lobule) consists of a respiratory bronchiole, alveolar ducts, and alveoli.
There are approximately 300 million alveoli in both lungs.
Each alveolus has an average diameter of about 0.2 mm.
Alveolar walls are thin with interconnecting capillaries between them, forming a sheet of flowing blood.
Gas exchange occurs between alveolar air and pulmonary blood in the terminal portions of the lungs.
All membranes involved are collectively known as the respiratory membrane or pulmonary membrane.

Respiratory Membrane (Alveolar-Capillary Membrane)

The respiratory membrane's ultrastructure includes several layers:
1. Fluid layer containing surfactant (reduces surface tension).
2. Alveolar epithelium (thin epithelial cells).
3. Epithelial basement membrane.
4. Thin interstitial space.
5. Capillary basement membrane (fused in places with the alveolar epithelial basement membrane).
6. Capillary endothelial membrane.
The overall thickness is about 0.2 micrometers in some areas, averaging 0.6 micrometers (excluding cell nuclei).
The total surface area is about 70 square meters in healthy men (equivalent to a 25 × 30-foot room).
The total blood quantity in lung capillaries at any given instant is 60 to 140 ml.
Pulmonary capillaries have an average diameter of about 5 micrometers, requiring red blood cells to squeeze through.
Red blood cell membrane usually touches the capillary wall, minimizing the amount of plasma the gases need to diffuse through.

Factors Affecting Gas Diffusion Rate

Factors influencing the rate of gas diffusion through the alveolar-capillary membrane:
- Thickness of the membrane.
- Surface area of the membrane.
- Diffusion coefficient of the gas.
- Partial pressure difference of the gas.
Increased membrane thickness (e.g., edema, fibrosis) hinders gas exchange.
Reduced surface area (e.g., emphysema, lung removal) impedes gas exchange.
The diffusion coefficient depends on the gas's solubility and the inverse square root of its molecular weight.
$CO2$ diffuses about 20 times faster than $O2$ . Oxygen diffuses about twice as rapidly as nitrogen.
The pressure difference is the partial pressure difference between the alveoli and the pulmonary capillary blood.
Net diffusion occurs from alveoli to blood for $O2$ and from blood to alveoli for $CO2$ .

Diffusing Capacity of the Respiratory Membrane

Diffusing capacity is the volume of gas that diffuses through the membrane per minute per mm Hg of partial pressure difference.

Diffusing Capacity for Oxygen

In young men at rest, the average diffusing capacity for $O_2$ is 21 ml/min per mm Hg.
With a mean $O_2$ pressure difference of 11 mm Hg, about 230 ml of oxygen diffuses per minute (equal to resting body usage).

Increased Oxygen Diffusing Capacity During Exercise

Diffusing capacity for $O_2$ increases up to threefold during exercise due to:
- Opening of dormant capillaries, increasing surface area.
- Improved ventilation-perfusion ratio.

Diffusing Capacity for Carbon Dioxide

The diffusing capacity for $CO2$ is hard to measure directly because the $Pco2$ difference is minimal (less than 1 mm Hg).
The diffusion coefficient of $CO2$ is about 20 times that of $O2$ .
Estimated diffusing capacity for $CO_2$ at rest is 400-450 ml/min per mm Hg, and during exercise, it's 1200-1300 ml/min per mm Hg.

Effect of Ventilation-Perfusion Ratio on Alveolar Gas Concentration

Alveolar $Po2$ and $Pco2$ are determined by:
- Alveolar ventilation rate.
- Transfer rate of $O2$ and $CO2$ .
Imbalances in ventilation and blood flow impair gas exchange.

The Ventilation-Perfusion Ratio – V/Q

$V$ (alveolar ventilation), $Q$ (blood flow).
Normal V/Q means ventilation and blood flow are normal.
V/Q of zero means ventilation is zero, but there is perfusion.
V/Q of infinity means there is ventilation but no perfusion.
No gas exchange occurs at ratios of zero or infinity.

Gas Exchange and Alveolar Partial Pressures When V/Q Is Normal

With normal ventilation and perfusion, gas exchange is optimal.
Alveolar $Po_2$ is normally 104 mm Hg (between inspired air at 149 mm Hg and venous blood at 40 mm Hg).
Alveolar $Pco_2$ is normally 40 mm Hg (between venous blood at 45 mm Hg and inspired air at 0 mm Hg).

Transport of Oxygen from the Lungs to the Body Tissues

Gases move by diffusion due to partial pressure differences.
$O2$ diffuses from alveoli to pulmonary capillary blood due to higher $Po2$ in the alveoli.
$O2$ diffuses from capillary blood to tissues due to higher $Po2$ in the capillary blood.
$CO2$ diffuses from cells into tissue capillaries due to higher intracellular $Pco2$ .
$CO2$ diffuses from pulmonary capillaries to alveoli due to higher $Pco2$ in the pulmonary capillary blood.

Diffusion of Oxygen from the Alveoli to the Pulmonary Capillary Blood

Alveolar $Po_2$ averages 104 mm Hg.
Venous blood entering the pulmonary capillary averages 40 mm Hg.
The initial pressure difference is 104 - 40 = 64 mm Hg.
Blood $Po_2$ rises rapidly and reaches almost 104 mm Hg after one-third of the capillary's length.

Uptake of Oxygen by the Pulmonary Blood During Exercise

During exercise, the body requires up to 20 times more oxygen.
Blood remains in the pulmonary capillary for less than half the normal time.
Blood becomes almost saturated with $O2$ due to a high safety factor. *The diffusing capacity for $O2$ increases almost threefold during exercise due to increased surface area and improved ventilation-perfusion ratio.

Transport of Oxygen in Arterial Blood

About 98% of blood entering the left atrium has $Po_2$ of 104 mm Hg.
About 2% of blood bypasses gas exchange (shunt flow).
The shunt blood has a $Po_2$ of approximately 40 mm Hg.
Venous admixture reduces the $Po_2$ of blood entering the aorta to about 95 mm Hg.

Diffusion of Oxygen from the Peripheral Capillaries into the Tissue Fluid

Arterial blood $Po_2$ in peripheral capillaries is 95 mm Hg.
Interstitial fluid $Po_2$ averages 40 mm Hg.
The pressure difference causes rapid diffusion of $O_2$ into tissues.
Capillary $Po2$ falls to 40 mm Hg, and venous blood $Po2$ is also about 40 mm Hg.

Increasing Tissue Metabolism Decreases Interstitial Fluid Po2

Increased $O2$ use reduces interstitial fluid $Po2$ .
Tissue $Po2$ is determined by the balance between $O2$ transport and usage.

Diffusion of Oxygen from Peripheral Capillaries to Tissue Cells

Intracellular $Po_2$ in peripheral tissues remains lower than in capillaries.
Intracellular $Po_2$ ranges from 5 to 40 mm Hg, averaging 23 mm Hg.
Only 1 to 3 mm Hg of $O_2$ pressure is required for full support of cellular chemical processes.

Diffusion of CO2 From Peripheral Tissue Cells into Capillaries and From Pulmonary Capillaries into Alveoli

$CO2$ diffuses in the opposite direction of $O2$ .
$CO2$ diffuses about 20 times as rapidly as $O2$ .
Pressure differences for $CO2$ diffusion are far less than for $O2$ .
*Intracellular $Pco2$ is 46 mm Hg; interstitial $Pco2$ is 45 mm Hg (1 mm Hg difference).
*Arterial blood $Pco2$ entering tissues is 40 mm Hg; venous blood $Pco2$ leaving tissues is 45 mm Hg.
*Pulmonary capillary $Pco2$ is 45 mm Hg; alveolar air $Pco2$ is 40 mm Hg (5 mm Hg difference).

Role of Hemoglobin in Oxygen Transport

About 97% of $O_2$ is transported bound to hemoglobin in red blood cells.
The remaining 3% is transported in dissolved form.

Reversible Combination of O2 With Hemoglobin

$O_2$ combines loosely and reversibly with heme.
At high $Po2$ , $O2$ binds with hemoglobin; at low $Po2$ , $O2$ is released.

Oxygen-Hemoglobin Dissociation Curve

The curve shows the percentage of hemoglobin bound with $O2$ as blood $Po2$ increases (percent saturation).
Systemic arterial blood with $Po2$ of 95 mm Hg has 97% $O2$ saturation.
Normal venous blood with $Po_2$ of 40 mm Hg has 75% hemoglobin saturation.

Maximum Amount of Oxygen That Can Combine With the Hemoglobin of the Blood

Normal blood contains 15 grams of hemoglobin per 100 ml.
Each gram of hemoglobin can bind with a maximum of 1.34 ml of $O_2$ .
15 * 1.34 = 20.1 ml of $O_2$ per 100 ml of blood (20 volume percent) when hemoglobin is 100% saturated.

Amount of Oxygen Released From Hemoglobin When Systemic Arterial Blood Flows Through Tissues

Arterial blood (97% saturated) contains about 19.4 ml $O_2$ /100 ml blood.
Venous blood (75% saturated) contains about 14.4 ml $O_2$ /100 ml blood.
Approximately 5 ml of $O_2$ is transported to tissues per 100 ml of blood flow.

Transport of Oxygen Is Markedly Increased During Strenuous Exercise

Muscle cells use $O2$ rapidly, reducing interstitial fluid $Po2$ to as low as 15 mm Hg.
At this low pressure, 4.4 ml $O_2$ remains bound per 100 ml blood.
19.4 - 4.4 = 15 ml of $O_2$ is delivered per 100 ml of blood flow (three times normal).
Cardiac output can increase 6-7 times, leading to a 20-fold increase in $O_2$ transport.

Hemoglobin “Buffers” Tissue Po2

Hemoglobin stabilizes $Po_2$ in tissues.
Under basal conditions, tissues require 5 ml $O2$ per 100 ml of blood, requiring $Po2$ to fall to 40 mm Hg.
Hemoglobin sets an upper limit on tissue Po2 at about 40 mm Hg.

Hemoglobin Helps Maintain Nearly Constant Po2 in the Tissues

During heavy exercise, extra $O2$ delivery is achieved with a small decrease in tissue $Po2$ because:
1. The steep slope of the dissociation curve
2. Increase in tissue blood flow caused by the decreased $Po_2$ .
Hemoglobin delivers $O_2$ to tissues at a pressure between 15 and 40 mm Hg.

Factors That Shift the Oxygen-Hemoglobin Dissociation Curve

A decrease in pH from 7.4 to 7.2 shifts the curve 15% to the right.
An increase in pH from 7.4 to 7.6 shifts the curve 15% to the left.
Factors shifting the curve to the right:
1. Increased $CO_2$ concentration.
2. Increased blood temperature.
3. Increased 2,3-biphosphoglycerate (BPG).

Increased Delivery of Oxygen to Tissues When CO2 and H + Shift the Oxygen-Hemoglobin Dissociation Curve—the Bohr Effect

*Blood passes through the tissues, $CO2$ diffuses from tissue cells into the blood. *This diffusion increases the blood $Pco2$ , which raises blood $H2CO3$ and $H^+$ concentration.

The $O2$ -hemoglobin dissociation curve shifts to the right and downward, delivering increased amounts of $O2$ to the tissues.

Metabolic Use of Oxygen by Cells Effect of Intracellular Po2 on Oxygen Usage Rate

*Cellular $Po2$ is more than 1 mm Hg, $O2$ availability is no longer a limiting factor in the rates of the chemical reactions

Whenever the intracellular $Po2$ is above 1 mm Hg, $O2$ usage rate becomes constant for any given concentration of ADP in the cell.
The rate of $O2$ usage changes in proportion to the change in ADP concentration. When adenosine triphosphate (ATP) is used in the cells to provide energy, it is converted into ADP. Under normal operating conditions, the rate of $O2$ usage by the cells is controlled ultimately by the rate of energy expenditure within the cells—that is, by the rate with which ADP is formed from ATP.

Metabolic Use of Oxygen by Cells Effect of Blood Flow on Metabolic Use of Oxygen

The total amount of $O_2$ available each minute for use in any given tissue is determined by:

*The quantity of $O_2$ that can be transported to the tissue in each 100 ml of blood
*The rate of blood flow.

Transport of Co2 in Blood

*Under normal resting conditions, an average of 4 ml of $CO_2$ are transported from the tissues to the lungs in each 100 ml of blood.

Chemical Forms in Which Co2 is Transported

A small portion of the $CO2$ is transported in the dissolved state to the lungs. The amount of $CO2$ dissolved in the fluid of the blood at 45 mm Hg is about 2.7 ml/dl (2.7 volume percent) and at 40 mm Hg is about 2.4 ml. Therefore, only about 0.3 ml of $CO2$ is transported in the dissolved form by each 100 ml of blood flow. This is about 7% of all the $CO2$ normally transported.

Transport of CO2 in Combination With Hemoglobin and Plasma Proteins—Carbaminohemoglobin

In addition to reacting with water, $CO_2$ reacts directly with amine radicals of the hemoglobin molecule to form the compound carbaminohemoglobin (CO2Hgb).
A small amount of $CO_2$ also reacts in the same way with the plasma proteins in tissue capillaries.
The quantity of $CO2$ that can be carried from the peripheral tissues to the lungs by carbamino combination with hemoglobin and plasma proteins is about 30% of the total quantity transported—that is, normally about 1.5 ml of $CO2$ in each 100 ml of blood.