Pulmonary diffusion

Gas exchange in the lungs, called pulmonary diffusion, serves two major functions:

• It replenishes the blood’s oxygen supply, which is depleted at the tissue level as it is used for oxidative energy production.
• It removes carbon dioxide from returning systemic venous blood.

Air is brought into the lungs during pulmonary ventilation, enabling gas exchange to occur between this air and the blood through pulmonary diffusion. Oxygen from the air diffuses from the alveoli into the blood in the pulmonary capillaries, and carbon dioxide diffuses from the blood into the alveoli in the lungs. The alveoli the grapelike clusters, or air sacs, at the ends of the terminal bronchioles.

Blood from most of the body returns through the vena cavae to the right side of the heart. From the right ventricle, this blood is pumped through the pulmonary artery to the lungs, ultimately working its way into the pulmonary capillaries. These capillaries form a dense network around the alveolar sacs. These vessels are so small that the red blood cells must pass through them in single file, such that each cell is exposed to the surrounding lung tissue. This is where pulmonary diffusion occurs.

Blood flow to the lungs at rest

At rest the lungs receive approximately 4 to 6L/min of blood flow, depending on body size. Because cardiac output from the right side of the heart approximates cardiac output from the left side of the heart, blood flow to the lungs matches blood flow to the systemic circulation. However, pressure and vascular resistance in the blood vessels in the lungs are different than in the system circulation. The mean pressure in the pulmonary artery is ~15 mmHg(systolic pressure is ~25 mmHg and diastolic pressure is ~8 mmHg) compared to the mean pressure in the aorta of ~95 mmHg. The pressure in the left atrium where blood is returning to the heart from the lungs is ~5 mmHg; thus there is not a great pressure difference across the pulmonary circulation(15-5 mmHg). Figure below illustrates the differences in pressures between the pulmonary and systemic circulation.

Recalling the discussion of blood flow in the cardiovascular system, pressure = flow x resistance. Since blood flow to the lungs is equal to that of the systemic circulation, and there is a substantially lower change in pressure across the pulmonary vascular system, resistance is proportionally lower compared to that in the systemic circulation. This is reflected in differences in the anatomy of the vessels in the pulmonary versus systemic circulation: the pulmonary blood vessels are thin walled, with relatively little smooth muscle.

Respiratory membrane

Gas exchange between the air in the alveoli and the blood in the pulmonary capillaries occurs across the respiratory membrane(also called the alveolar-capillary membrane). This membrane, depicted in the picture below, is composed of:

• The alveolar wall
• The capillary wall
• Their basement membranes.

The primary function of these membranous surfaces is for gas exchange. The respiration membrane is very thin, measuring only 0.5 to 4.0 micrometres. As a result, the gases in the nearly 300 million alveoli are in close proximity to the blood circulating through the capillaries.

Partial pressure of gases

The air we breathe is a mixture of gases. Each exerts a pressure in proportion to its concentration in the gas mixture. The individual pressures from each gas in a mixture are reffered to as partial pressures. According to Dalton’s law, the total pressure of a mixture of gases equals the sum of the partial pressures of the individual gases in that mixture.

Consider the air we breathe. It is composed of 79.04% nitrogen(N₂), 20.93% oxygen(O₂), and 0.03% carbon dioxide(CO₂). These percentages remain constant regardless of altitude. At sea level, the atmospheric(or barometric) pressure is approximately 760 mmHg, which is also referred to as standard atmospheric pressure. Thus, if the total atmospheric pressure is 760 mmHg, then the partial pressure of nitrogen(PN₂) in air is 600.7 mmHg(79.04% of the total 760 mmHg pressure). Oxygen’s partial pressure(PO₂) is 159.1 mmHg(20.93% of 760 mmHg), and carbon dioxide’s partial pressure(PCO₂) is 0.2 mmHg(0.03% of 760 mmHg).

In the human body, gases are usually dissolved in fluids, such as blood plasma. According to Henry’s law, gases dissolve in liquids in proportion to their partial pressures, depending also on their solubilities in the specific fluids and on the temperature. A gas’s solubility in blood is a constant, and blood temperature also remains relatively constant at rest. Thus, the most critical factor for gas exchange between the alveoli and the blood is the pressure gradient between the gases in the two areas.

Gas exchange in the alveoli

Differences in the partial pressures of the gases in the alveoli and the gases in the blood create a pressure gradient across the respiratory membrane. This forms the basis of gas exchange during pulmonary diffusion. If the pressures on each side of the membrane were equal, the gases would be at equilibrium and would not move. But the pressures are not equal, so gases move according to partial pressure gradients.

Oxygen exchange

The PO₂ of air outside the body at standard atmospheric pressure is 159 mmHg. But this pressure decreases to about 105 mmHg when air is inhaled and enters the alveoli, where it is moistened and mixes with the air in the alveoli. The alveolar air is saturated with water vapor(which has its own partial pressure) and contains more carbon dioxide than the inspired air. Both the increased water vapor pressure and increased partial pressure of carbon dioxide contribute to the total pressure in the alveoli. Fresh air that ventilates the lungs is constantly mixed with the air in the alveoli while some of the alveolar gases are exhaled to the environment. As a result, alveolar gas concentrations remain relatively stable.

The blood, stripped of much of its oxygen by the tissues, typically enters the pulmonary capillaries with a PO₂ of about 40 mmHg(see figure below). This is about 60 to 65 mmHg less than the PO₂ in the alveoli. In other words, the pressure gradient for oxygen across the respiratory membrane is typically under 65 mmHg. As noted earlier, this pressure gradient drives the oxygen from the alveoli into the blood to equilibrate the pressure of the oxygen on each side of the membrane.

The PO₂ in the alveoli stays relatively constant at about 105 mmHg. As the deoxygenated blood enters the pulmonary artery, the PO₂ in the blood is only about the 40 mmHg. But as the blood moves along the pulmonary capillaries, gas exchange occurs. By the time the pulmonary blood reaches the venous end of these capillaries, the PO₂ in the blood equals that in the alveoli(approximately 105 mmHg), and the blood is now considered to be saturated with oxygen as its full carrying capacity. The blood leaving the lungs through the pulmonary veins and subsequently returning to the systemic(left) side of the heart has a rich supply of oxygen to deliver to the tissues. Notice, however, that the PO₂ in the pulmonary vein is 100 mmHg, not the 105 mmHg found in the alveolar air and pulmonary capillaries. This difference is attributable to the fact that about 2% of the blood is shunted from the aorta directly to the lung to meet the oxygen needs of the lung itself. This blood has a lower PO₂ and reenters the pulmonary vein along with fully saturated blood returning to the left atrium that has just completed gas exchange. This blood mixes and thus decreases the PO₂ of blood returning to the heart.

Diffusion through tissues is described by Fick’s law(see figure below). Fick’s law states that the rate of diffusion through a tissue such as the respiratory membrane is proportional to the surface area and the difference in the partial pressure of gas between the two sides of the tissue. The rate of diffusion is also inversely proportional to the thickness of the tissue in which the gas must diffuse. Additionally, the diffusion constant, which is unique to each gas, influences the rate of diffusion across the tissue. Carbon dioxide has a much lower diffusion constant than oxygen; therefore, even though there is not as great a difference between alveolar and capillary partial pressure of carbon dioxide as there is for oxygen, carbon dioxide still diffuses easily.

The rate at which oxygen diffuses from the alveoli into the blood is reffered to as the oxygen diffusion capacity and is expressed as the volume of oxygen that diffuses through the membrane each minute for a pressure difference of 1 mmHg. At rest, the oxygen diffusion capacity is about 21ml of oxygen per minute per 1 mmHg of pressure difference between the alveoli and the pulmonary capillary blood. Although the partial pressure gradient between venous blood coming into the lung and the alveolar air is about 65 mmHg(105 mmHg – 40 mmHg), the oxygen diffusion capacity is calculated on the basis of the mean pressure in the pulmonary capillary, which has a substantially higher PO₂. The gradient between the mean partial pressure of the pulmonary capillary and the alveolar air is approximately 11 mmHg, which would provide a diffusion of 231ml of oxygen per minute through the respiratory membrane. During maximal exercise, the oxygen difference fusion capacity may increase by up to three times the resting rate, because blood is returning to the lungs severely desaturated and thus there is a greater partial pressure gradient from the alveoli to the blood. In fact, rates of more than 80 ml/min have been observed among highly trained athletes.

The increase in oxygen diffusion capacity from rest to exercise is caused by a relatively inefficient, sluggish circulation through the lungs at rest, which results primarily from limited perfusion of the upper regions of the lungs attributable to gravity. If the lung is divided into three zones as depicted in the figure below, at rest only the bottom third(zone 3) of the lung is perfused with blood. During exercise, however, blood flow through the lungs is greater, primarily as a result of elevated blood pressure, which increases lung perfusion.

Carbon dioxide exchange

Carbon dioxide, like oxygen, moves along a pressure gradient. As shown in the figure 3 of this draw, the blood passing from the right side of the heart through the alveoli has a PCO₂ of about 46 mmHg. Air in the alveoli has a PCO₂ of about 40 mmHg. Although this results in a relatively small pressure gradient of only about 6 mmHg, it is more than adequate to allow for exchange of CO₂. Carbon dioxide’s diffusion coefficient is 20 times greater than that of oxygen, so CO₂ can diffuse across the respiratory membrane much more rapidly.

The partial pressures of gases involved in pulmonary diffusion are summarized in the table below. Note that the total pressure in the venous blood is only 706 mmHg, 54 mmHg lower than the total pressure in dry air and alveolar air. This is the result of a much greater decrease in PO₂ compared with the increase in PCO₂ as the blood goes through the body’s tissues.

Partial pressure of gases at sea level
		Partial pressure (mmHg)
Gas	% in dry air	dry air	alveolar air	arterial blood	venous blood	diffusion gradient
H2O	0.00	0	47	47	47	0
O2	20.93	159.1	105	100	40	60
CO2	0.03	0.2	40	40	46	6
N2	79.04	600.7	568	573	573	0
Total	100.00	760	760	760	706	0