Blood Gases

Definition

Blood gases are defined as the mixture of gases, including oxygen (O₂), carbon dioxide (CO₂), and nitrogen (N₂), dissolved in the fluid fraction of blood.

Description

Oxygen from the air is transported from the lungs to all tissues of the body, where it is needed for metabolism; and carbon dioxide, a byproduct of metabolism, is taken from the tissues to the lungs to be eliminated.

Respiration

The overall process of delivering oxygen to the tissues and carrying carbon dioxide away is called respiration. When the blood reaches the tissues, oxygen diffuses into the cells, and carbon dioxide diffuses from the cells into the blood. In the lungs, the air enters a branching complex of multiple air sacs, called alveoli, where tiny capillaries separate the air from the red blood cells by only a very thin membrane, about 0.3 μm thick. During respiration the inspired air is filtered and moistened by the nose and tracheal linings and is completely saturated with water vapor by the time it enters the alveolar sac.

In the alveolus, oxygen diffuses into the blood, and carbon dioxide diffuses out of the blood to mix with the alveolar air. Diffusion is a very rapid process, and the gases do not have time to totally equilibrate across the alveolar membrane. A small pressure difference for each gas develops. About 2% of the blood flow through the lungs bypasses the pulmonary capillaries and does not become oxygenated; thus, the partial pressure of oxygen is somewhat higher in the alveolus than in the blood. This pressure difference, calculated for the lung as a whole, is called the arterial-alveolar (A-a) gradient.

Composition of gases in air

Dry air is made up of 20.98% oxygen, 0.04% carbon dioxide, 78.06% nitrogen, and 0.92% other gases (mostly argon). In blood-gas analysis, the content of the gases oxygen and carbon dioxide are reported in terms of their partial pressures, with normal values for oxygen (PO₂) of 75 mm to 100 mm of mercury (mm Hg) and for carbon dioxide (PCO₂)of35 to 45 mm Hg. The partial pressure of water vapor in the lung, where the air is completely water-saturated, at body temperature (98.6°F, or 37°C) is 47 milliliters of mercury (mm Hg).

Function

As blood circulates through the body, oxygen diffuses from the area of higher partial pressure. The blood moves toward the area of lower partial pressure, the cells, and carbon dioxide diffuses from the cells into the blood. In the lung, oxygen diffuses into the blood, where it is taken up by hemoglobin, and carbon dioxide diffuses out of the blood, to be exhaled.

Oxygen

Oxygen in the blood is carried by hemoglobin. The hemoglobin content of normal blood is about 15 to 16 grams per 100 ml, and each gram of hemoglobin binds about 1.34 ml of oxygen gas. Thus, arterial blood contains about 20 ml of oxygen per 100 ml when fully saturated. The volume of oxygen in the blood, the O₂ content, is dependent on the hemoglobin concentration and does not provide as good a measure of lung function as the partial pressure of oxygen PO₂) in arterial blood.

The amount of oxygen in the blood relative to the carrying capacity of the hemoglobin is called the oxygen saturation. The oxygen saturation of hemoglobin is directly proportional to the PO₂; the relationship is not linear but is described by a sigmoidal (S-shape) curve. Oxygen saturation is affected by the acid-base status of the blood: at a given PO₂, the degree of oxygen saturation may be lowered by increasing the acidity of the blood. Oxygen saturation is expressed as a percentage; hemoglobin in arterial blood is about 97% saturated, while the more acidic venous blood is about 75% saturated.

Carbon dioxide

Carbon dioxide is formed in the cells during aerobic metabolism and diffuses into the capillaries, where only a small amount remains dissolved. It enters the red blood cells, where carbonic anhydrase quickly catalyzes its conversion to carbonic acid, which dissociates to hydrogen ion and bicarbonate. About two-thirds of the bicarbonate diffuses out into the plasma and is replaced by chloride in the red cell. The hydrogen ion binds to hemoglobin, and is transported to the lungs.

Arterial blood normally contains an amount of bicarbonate that is the equivalent of about 50 ml of carbon dioxide gas per 100 ml of blood. About 5 ml of additional carbon dioxide enters the blood in the capillaries and is converted to bicarbonate and hydrogen ion, making the blood more acidic and causing the pH to drop from 7.4 to 7.36. On reaching the lungs, the bicarbonate and hydrogen ion are converted back to carbon dioxide, which diffuses into the alveoli for exhalation. Over a period of 24 hours at rest, about 200 ml of carbon dioxide, the equivalent of 12,500 milliequivalents of acid, is produced by metabolism and eliminated via the lungs. The carbonic-acid concentration can change in seconds in response to hypoor hyperventilation, while changes in the bicarbonate concentration take much longer—hours or days—because elimination by the kidney is relatively slow.

Carbon monoxide

Small amounts of carbon monoxide (CO) are produced during metabolism. Carbon monoxide binds tightly to hemoglobin to form a CO-hemoglobin complex called carboxyhemoglobin in which the binding of oxygen molecules is prevented. Thus, carbon monoxide reduces the oxygen saturation of hemoglobin at any given PO₂. City dwellers and smokers are exposed to a much higher level of carbon monoxide in the air: in heavy smokers, as much as 10% of hemoglobin may be carboxyhemoglobin.

Nitrogen and other gases

The nitrogen and other gases inhaled are, under normal circumstances, inert and play no role in human health. A painful and potentially fatal condition, called decompression sickness or the bends, can be caused by formation of nitrogen bubbles in the blood and tissues by moving too quickly from areas of higher atmospheric pressures to lower pressures, such as when deep-sea divers return too quickly to the surface of the water.

Role in human health

Acid-base balance in the blood

Carbon dioxide in the blood is transported as bicarbonate, since carbon dioxide combines with water to form carbonic acid:

CO₂ + H₂O = H₂CO₃

which is in equilibrium with hydrogen ions and bicarbonate:

H₂CO₃ = H⁺ + HCO₃⁻

The concentration of hydrogen ions (H⁺) determines the pH, a measure of the acidity, of the blood. The carbonic acid-bicarbonate equilibrium is an example of a buffer system and is involved in the maintenance of the acid-base balance in the body. The pH of the blood is related to the ratio of bicarbonate to carbonic acid, which is normally about 20:1. The carbonic acid-bicarbonate buffering system is extended by the body's ability to convert carbonic acid to carbon dioxide (catalyzed by the enzyme carbonic anhydrase) and the removal of CO2 in respired air. In addition, the body has the ability to eliminate hydrogen or bicarbonate ions via the kidneys to maintain pH.

Since most body systems function best at a pH near 7.4, the pH of the body must be maintained within a narrow range. When the blood pH is higher or lower than the normal level of 7.35 to 7.45, enzymes may function less effectively or not at all, nerve and muscle activity weakens, and finally all metabolic activity is undermined.

Proteins also function as buffers; hemoglobin in particular is an important buffering agent in the blood. Oxygen-bound hemoglobin is a stronger acid than hemoglobin without oxygen, and tends to release hydrogen ions; when hemoglobin is exposed to the lower oxygen concentrations in the capillaries, oxygen is released, the hemoglobin becomes a weaker acid, and hydrogen ions are taken up. The relationship between pH and the ability of hemoglobin to bind oxygen, which is reflected in saturation levels of hemoglobin in arterial versus venous blood, is known as the Bohr effect.

Buffer base and base excess

The buffer base is the sum of all anionic buffer components in the blood, including bicarbonate, sulfates, and phosphates. The base excess refers to how much a patient's buffer base is higher than normal, and is expressed in terms of the amount of acid in milliequivalents per liter (mEq/L) that would have to be added to the patient's blood to bring it to a normal pH of 7.4. Many physicians rely only on the difference between the patient's bicarbonate and an average value for bicarbonate of 24 mEq/L as an indication of the need for bicarbonate replacement. However, the base excess is more meaningful, since other buffers are taken into account and is accurate also in anemic patients, where the buffering capacity of hemoglobin is diminished. Base excess can be negative in value for acidotic patients; that is, acid would have to be taken away to bring the pH to normal.

The clinical determination of how much bicarbonate to administer in the treatment of severe acidosis is usually based on the base excess of the blood. The base excess of blood, however, is not a true indication of the base excess of the extracellular fluid (ECF) of the whole body. Only blood contains hemoglobin, and other extracellular fluids have different protein contents and buffering capacities. Furthermore, fluid distribution in the body varies with the state of hydration, and ECF as a percentage of body weight varies with age and fat content. In general, however, the recommendation for bicarbonate therapy is 0.1 to 0.2 mEq × body weight × base excess.

Control of respiration

The levels of blood gases act to control the rate of respiration. The aortic and carotid bodies, special chemical receptors near the aorta and carotid arteries, respond to changes in the levels of acid, carbon dioxide, or oxygen, stimulating the brain respiratory centers in the brain stem to regulate the speed and depth of breathing. When blood acid is increased, such as during diabetic ketoacidosis, or when there is a rise in CO₂ during the increased metabolism of exercise, respiration is stimulated. The respiratory centers in the brain also respond directly to increases in PCO₂ and stimulate respiration. The resulting deep, rapid breathing acts to mix alveolar air with CO₂-poor air to decrease the carbon dioxide in the blood as it passes by the alveolus, and the reduction in CO₂ returns the blood toward normal. Lack of oxygen can also weakly stimulate respiration. Oxygen levels usually play little role in the regulation of respiration in healthy individuals at normal altitudes, but at very low PO₂ (i.e., <60 mm Hg), as in patients suffering from severe chronic bronchitis and emphysema, respiration can be stimulated.

Common diseases and disorders

Disorders involving the levels of blood gases are primarily diagnosed on the basis of disturbances in the acid-base balance as acidosis or alkalosis. Acid-base disorders may be respiratory or nonrespiratory (metabolic) in origin, or of mixed origin.

Acidosis with elevated PCO₂ is classified as respiratory acidosis. Causes include:

• airway obstruction due to chronic conditions such as bronchitis or emphysema, or acute causes such as bronchospasm or aspiration of foreign material
• neuromuscular diseases such as poliomyelitis, motorneuron disease, or tetanus, or due to neurotoxins such as botulin or curare
• pulmonary diseases including pneumonia and pulmonary fibrosis, and extrapulmonary thoracic disorders such multiple broken ribs or kyphoscoliosis
• respiratory-center depression due to cerebral trauma or tumor, or secondary to anesthesia or application of sedatives

Alkalosis with depressed PO₂ is classified as respiratory alkalosis. Causes include:

• hypoxia due to high altitude, anemia, or pulmonary disease
• hyperventilation, whether voluntary or secondary to trauma, infection, cerebral tumor, or ingestion of a respiratory stimulant
• pulmonary edema or embolism
• artificial overventilation

Acidosis with depressed PCO₂ and bicarbonate is classified as nonrespiratory, or metabolic, acidosis. Causes include:

• diabetic or alcoholic ketoacidosis
• acid poisoning, including secondary to alcohol poisoning
• decreased elimination of acid due to renal failure
• loss of bicarbonate, such as during diarrhea

Alkalosis with elevated PO₂ and bicarbonate is classified as nonrespiratory, or metabolic, alkalosis. Causes include:

• loss of unbuffered acid due to gastrointestinal and/or renal disturbances
• chronic ingestion of antacid preparations, or a highfruit, low-protein diet

A low value for PO₂ (hypoxemia) is also indicative of respiratory disturbance. Hypoxemia may be caused by:

• low inspired levels of oxygen, such as at high altitude
• hypoventilation due to respiratory depression or neuromuscular disease
• mixing of arterial and venous blood, as in cyanotic congenital heart disease
• impaired oxygen diffusion as in pulmonary fibrosis
• chronic diseases of airway obstruction, such as bronchitis and emphysema

KEY TERMS

Acid— A chemical compound that reacts with a base to form a salt, that can give off hydrogen ions in water solution, or that contains an atom that can accept a pair of electrons from a base.

Acidosis— A blood condition in which the pH is <7.35 and is below normal.

Alkalosis— A blood condition in which the pH is >7.45 and is above normal.

Alveoli— Air sacs of the lungs located at the termini of the bronchial passageways.

Base— A chemical compound that reacts with an acid to form a salt, that takes up or accepts protons, or that contains an atom with a free pair of electrons to be donated to an acid.

Buffer— A chemical substance that resists changes in pH in response to changes in acid and base concentration; a buffer system consists of a weak acid or weak base in combination with its salt.

Carbonic anhydrase— An enzyme that catalyzes the reversible reaction of carbon dioxide with water to form carbonic acid in red blood cells.

Hemoglobin— The red-colored, iron-containing protein in red blood cells that carries oxygen to the tissues.

Ketoacidosis— An excessive level of acid accompanied by an increase in the level of ketones in blood that occurs as a complication of diabetes mellitus; ketones are substances normally processed by the liver from fats.

Metabolism— The physical and chemical processes carried out by an organism to produce, maintain, and destroy material substances and to make energy available.

pH— An exponential measurement scale for expressing the concentration of acid in solution pH = −log [H⁺].

Resources

BOOKS

Marshall, William J. Clinical Chemistry, Fourth Edition. Edinburgh, London, New York, Philadelphia, St. Louis, and Toronto: Mosby, 2000.

OTHER

Argyle, B. Mad Scientist Software, Blood Gases Computer Program Manual. 1996 Mad Scientist Software, Alpine UT. 〈http://www.madsci.com/manu/gas_acid.htm〉.

HealthCentral Web site. 1998 A.D.A.M. Software. 〈http://www.healthcentral.com/mhc/top/003855.cfm〉.