Homeostasis Module

Blood Gases

Learning Objectives

By the end of this section, you will be able to:

  • Describe the mechanisms that drive gas exchange
  • Describe the process of external and internal respiration
  • Define the  hemoglobin-oxygen dissociation curve
  • Explain the factors that affect hemoglobin-oxygen binding

The purpose of the respiratory system is to perform gas exchange. Pulmonary ventilation provides air to the alveoli for this gas exchange process. Respiration occurs at the respiratory membrane, where the alveolar and capillary walls meet, gases move across the membranes, with oxygen entering the bloodstream and carbon dioxide exiting. It is through this mechanism that blood is oxygenated and carbon dioxide, the waste product of cellular respiration, is removed from the body.

Gas Exchange

In order to understand the mechanisms of gas exchange in the lung, it is important to understand the underlying principles of gases and their behavior.

Gas molecules exert force on the surfaces with which they are in contact; this force is called pressure. In natural systems, gases are normally present as a mixture of different types of molecules. For example, the atmosphere consists of oxygen, nitrogen, carbon dioxide, and other gaseous molecules, and this gaseous mixture exerts a certain pressure referred to as atmospheric pressure. Partial pressure (Px) is the pressure of a single type of gas in a mixture of gases. For example, in the atmosphere, oxygen exerts a partial pressure, and nitrogen exerts another partial pressure, independent of the partial pressure of oxygen (Figure 1). Total pressure is the sum of all the partial pressures of a gaseous mixture.

The left panel of this figure shows a canister of oxygen. The middle panel shows a canister of nitrogen. The right panel shows a canister containing a mixture of oxygen and nitrogen. A pressure gauge on each container shows the pressure exerted by the gas in that container.
Figure 1. Partial and Total Pressures of a Gas. Partial pressure is the force exerted by a gas. The sum of the partial pressures of all the gases in a mixture equals the total pressure.

Partial pressure is extremely important in predicting the movement of gases. Recall that gases tend to equalize their pressure in two regions that are connected. A gas will move from an area where its partial pressure is higher to an area where its partial pressure is lower. In addition, the greater the partial pressure difference between the two areas, the more rapid is the movement of gases.

Gas exchange occurs at two sites in the body: in the lungs, where oxygen is picked up and carbon dioxide is released at the respiratory membrane, and at the tissues, where oxygen is released and carbon dioxide is picked up. The actual exchange of gases occurs due to simple diffusion. Energy is not required to move oxygen or carbon dioxide across membranes. Instead, these gases follow pressure gradients that allow them to diffuse. The anatomy of the lung maximizes the diffusion of gases: The respiratory membrane, also known as the air-blood barrier, (Figure 2) is highly permeable to gases as the respiratory and blood capillary membranes are very thin. Additional factors that affect gas diffusion include surface area of total respiratory membrane, and partial pressure difference across the respiratory membrane.

Figure 2. Respiratory Membrane, composed of 1. surfactant, 2. type 1 alveolar (epithelial) cell, 3. basement membrane, 4. interstitial space, 5. basement membrane, 6. endothelium.

External Respiration

External respiration occurs as a function of partial pressure differences in oxygen and carbon dioxide between the alveoli and the blood in the pulmonary capillaries (Figure 3). Although a small amount of the oxygen is able to dissolve directly into plasma from the alveoli, most of the oxygen (>98%) is picked up by erythrocytes (red blood cells) and binds reversibly with hemoglobin. Carbon dioxide is released in the opposite direction of oxygen, from the blood to the alveoli. Some (~30%) of the carbon dioxide is returned on hemoglobin (carbamino-Hb), but can also be dissolved in plasma (~10%) or is present as a converted form (~60% in the form of bicarbonate).

This figure shows the pathway in which external respiration takes place. The exchange of oxygen and carbon dioxide between the alveolus and blood plasma is detailed.
Figure 3. External Respiration. In external respiration, oxygen diffuses across the respiratory membrane from the alveolus to the capillary, whereas carbon dioxide diffuses out of the capillary into the alveolus.

Although the solubility of oxygen in blood is not high, there is a drastic difference in the partial pressure of oxygen in the alveoli versus in the blood of the pulmonary capillaries. This difference is about 64 mm Hg: The partial pressure of oxygen in the alveoli is about 104 mm Hg, whereas its partial pressure in the blood of the capillary is about 40 mm Hg. This large difference in partial pressure creates a very strong pressure gradient that causes oxygen to rapidly cross the respiratory membrane from the alveoli into the blood.

The partial pressure of carbon dioxide is also different between the alveolar air and the blood of the capillary. However, the partial pressure difference is less than that of oxygen, about 5 mm Hg. The partial pressure of carbon dioxide in the blood of the capillary is about 45 mm Hg, whereas its partial pressure in the alveoli is about 40 mm Hg. However, the solubility of carbon dioxide is much greater than that of oxygen—by a factor of about 20—in both blood and alveolar fluids. As a result, the relative concentrations of oxygen and carbon dioxide that diffuse across the respiratory membrane are similar.

Internal Respiration

Internal respiration is gas exchange that occurs at the level of body tissues (Figure 4). Similar to external respiration, internal respiration also occurs as simple diffusion due to a partial pressure gradient. However, the partial pressure gradients are opposite of those present at the respiratory membrane. The partial pressure of oxygen in tissues is low, about 40 mm Hg, because oxygen is continuously used for cellular respiration. In contrast, the partial pressure of oxygen in the blood is about 100 mm Hg. This creates a pressure gradient that causes oxygen to dissociate from hemoglobin, diffuse out of the blood, cross the interstitial space, and enter the tissue.

Considering that cellular respiration continuously produces carbon dioxide, the partial pressure of carbon dioxide is lower in the blood than it is in the tissue, causing carbon dioxide to diffuse out of the tissue, cross the interstitial fluid, and enter the blood. It is then carried back to the lungs either bound to hemoglobin, dissolved in plasma, or in a converted form. The blood is then pumped back to the lungs to be oxygenated once again during external respiration.

This diagram details the pathway of internal respiration. The exchange of oxygen and carbon dioxide between a red blood cell and a tissue cell is shown.
Figure 4. Internal Respiration. Oxygen diffuses out of the capillary and into cells, whereas carbon dioxide diffuses out of cells and into the capillary.

Bicarbonate Buffer

A large fraction—about 70 percent—of the carbon dioxide molecules that diffuse into the blood is transported to the lungs as bicarbonate. Most bicarbonate is produced in erythrocytes after carbon dioxide diffuses into the capillaries, and subsequently into red blood cells. Carbonic anhydrase (CA) causes carbon dioxide and water to form carbonic acid (H2CO3), which dissociates into two ions: bicarbonate (HCO3) and hydrogen (H+). The following formula depicts this reaction:

CO2 + H2O CA ↔ H2CO3↔H+ + HCO3−

Bicarbonate tends to build up in the erythrocytes, so that there is a greater concentration of bicarbonate in the erythrocytes than in the surrounding blood plasma. At the pulmonary capillaries, the chemical reaction that produced bicarbonate (shown above) is reversed, and carbon dioxide and water are the products. Hydrogen ions and bicarbonate ions join to form carbonic acid, which is converted into carbon dioxide and water by carbonic anhydrase. Carbon dioxide diffuses out of the erythrocytes and into the plasma, where it can further diffuse across the respiratory membrane into the alveoli to be exhaled during pulmonary ventilation.

Oxygen Dissociation from Hemoglobin

Partial pressure is an important aspect of the binding of oxygen to and disassociation from heme. An oxygen–hemoglobin dissociation curve is a graph that describes the relationship of partial pressure to the binding of oxygen to heme and its subsequent dissociation from heme (Figure 5). Remember that gases travel from an area of higher partial pressure to an area of lower partial pressure. In addition, the affinity of an oxygen molecule for heme increases as more oxygen molecules are bound. Therefore, the partial pressure of oxygen plays a major role in determining the degree of binding of oxygen to heme at the site of the respiratory membrane, as well as the degree of dissociation of oxygen from heme at the site of body tissues.

The top panel of this figure shows a graph with oxygen saturation of the y-axis and partial pressure of oxygen on the x-axis.The middle panel shows oxygen saturation versus partial pressure of oxygen as a function of pH.

The bottom panel shows the same relationship as a function of temperature.
Figure 5. Oxygen-Hemoglobin Dissociation and Effects of pH and Temperature. These three graphs show (a) the relationship between the partial pressure of oxygen and hemoglobin saturation, (b) the effect of pH on the oxygen–hemoglobin dissociation curve, and (c) the effect of temperature on the oxygen–hemoglobin dissociation curve.

Factors other than partial pressure also affect the oxygen–hemoglobin saturation/dissociation curve. For example, a higher temperature promotes hemoglobin and oxygen to dissociate faster, whereas a lower temperature inhibits dissociation (see Figure 5, middle). However, the human body tightly regulates temperature, so this factor may not affect gas exchange throughout the body. The exception to this is in highly active tissues, which may release a larger amount of energy than is given off as heat. As a result, oxygen readily dissociates from hemoglobin, which is a mechanism that helps to provide active tissues with more oxygen.

Certain hormones, such as androgens, epinephrine, thyroid hormones, and growth hormone, can affect the oxygen–hemoglobin saturation/disassociation curve by stimulating the production of a compound called 2,3-bisphosphoglycerate (BPG) by erythrocytes. BPG is a byproduct of glycolysis. Because erythrocytes do not contain mitochondria, glycolysis is the sole method by which these cells produce ATP. BPG promotes the disassociation of oxygen from hemoglobin. Therefore, the greater the concentration of BPG, the more readily oxygen dissociates from hemoglobin, despite its partial pressure.

The pH of the blood is another factor that influences the oxygen–hemoglobin saturation/dissociation curve (see Figure 5). The Bohr effect is a phenomenon that arises from the relationship between pH and oxygen’s affinity for hemoglobin: A lower, more acidic pH promotes oxygen dissociation from hemoglobin. In contrast, a higher, or more basic, pH inhibits oxygen dissociation from hemoglobin. The greater the amount of carbon dioxide in the blood, the more molecules that must be converted, which in turn generates hydrogen ions and thus lowers blood pH. Furthermore, blood pH may become more acidic when certain byproducts of cell metabolism, such as lactic acid, carbonic acid, and carbon dioxide, are released into the bloodstream.

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Path 300 - Clinical Chemistry Copyright © by Deb Chen is licensed under a Creative Commons Attribution 4.0 International License, except where otherwise noted.

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