Structure and Function of the Mammalian Respiratory System

Structure and Function of the Mammalian Respiratory System
Air enters a mammalian respiratory system through nostrils (external nares), passes through a nasal chamber, lined with mucus-secreting epithelium, and then through internal nares, nasal openings connected to the pharynx. Here, where pathways of digestion and respiration cross, inhaled air leaves the pharynx by passing into a narrow opening, the glottis; food enters the esophagus to pass to the stomach (see Figure 34-10,). The glottis opens into the larynx, or voice box, and then into the trachea, or windpipe. The trachea branches into two bronchi, one to each lung (Figure 33-22). Within the lungs each bronchus divides and subdivides into small tubes (bronchioles) that lead via alveolar ducts to the air sacs (alveoli) (Figure 33-22). The singlelayered endothelial walls of the alveoli are thin and moist to facilitate exchange of gases between air sacs and adjacent blood capillaries. Air passageways are lined with both mucussecreting and ciliated epithelial cells, which play an important role in conditioning the air before it reaches the alveoli. Partial cartilage rings in the walls of the tracheae, bronchi, and even some of the bronchioles prevent those structures from collapsing.

In its passage to the air sacs, air undergoes three important changes: (1) it is filtered free from most dust and other foreign substances, (2) it is warmed to body temperature, and (3) it is saturated with moisture.

The lungs consist of a great deal of elastic connective tissue and some muscle. They are covered by a thin layer of tough epithelium known as the visceral pleura. A similar layer, the parietal pleura, lines the inner surface of the walls of the chest (Figure 33-22). The two layers of the pleura are in contact and slide over one another as the lungs expand and contract. The “space” between the pleura, called the pleural cavity, maintains a partial vacuum, which helps keep the lungs expanded to fill the pleural cavity. Therefore no real pleural space exists; the two pleura rub together, lubricated by tissue fluid (lymph). The chest cavity is bounded by the spine, ribs, and breastbone, and floored by the diaphragm, a dome-shaped, muscular partition between the chest cavity and abdomen. A muscular diaphragm is found only in mammals.

Ventilating the lungs
The chest cavity is an air-tight chamber. Inspiration pulls the ribs upward, flattens the diaphragm, and enlarges the chest cavity (Figure 33-24). The resultant increase in volume of the chest cavity causes air pressure in the lungs to fall below atmospheric pressure: air rushes in through passageways to equalize the pressure. Normal expiration is a less active process than inspiration. When the muscles relax, the ribs and diaphragm return to their original position, and the chest cavity decreases in size, the elastic lungs deflate, and air exits (Figure 33-24).



How Breathing Is Coordinated
Breathing is normally involuntary and automatic but can come under voluntary control. Neurons in the medulla of the brain regulate normal, quiet breathing. They spontaneously produce rhythmical bursts that stimulate contraction of the diaphragm and external intercostal muscles. However, respiration must adjust itself to changing requirements of the body for oxygen. Oddly, carbon dioxide rather than oxygen has the greatest effect on respiratory rate because under normal conditions arterial oxygen does not decline enough to stimulate oxygen receptors. Even a small rise in carbon dioxide level in the blood, however, has a powerful effect on respiratory activity. Actually, the stimulatory effects of carbon dioxide are due in part to an increase in hydrogen ion concentration in cerebrospinal fluid.

This reaction shows that carbon dioxide combines with water to form carbonic acid. Carbonic acid then dissociates to release hydrogen ions, making the cerebrospinal fluid more acidic, and stimulating respiratory receptors in the medulla of the brain. Both rate and depth of respiration increase.

It is well known that swimmers can remain submerged much longer if they vigorously hyperventilate first to blow off carbon dioxide from the lungs, thereby delaying the overpowering urge to surface and breathe.The practice is dangerous because blood oxygen is depleted just as rapidly as without prior hyperventilation, and the swimmer may lose consciousness when the oxygen supply to the brain drops below a critical point. Several documented drownings among swimmers attempting long underwater swimming records have been caused by this practice.

Gaseous Exchange in Lungs and Body Tissues: Diffusion and Partial Pressure
Air (the atmosphere) is a mixture of gases: about 71% nitrogen, 20.9% oxygen, in addition to fractional percentages of other gases, such as carbon dioxide (0.03%). Gravity attracts the mass of the atmosphere to the earth. At sea level the atmosphere exerts a hydrostatic pressure due to gravity equal to the weight of a column of mercury (Hg) 760 mm high. Thus we can speak of atmospheric pressure (1 atm) as being equal to 760 mm Hg. But because air is not a single gas but a mixture, part of the 760 mm Hg pressure (partial pressure) is due to each component gas. For example, the partial pressure of oxygen is 0.209 × 760 ×159 mm, and that for carbon dioxide is 0.0003 × 760 ×0.23 mm in dry air. (In fact, atmospheric air is never completely dry, and the varying amount of water vapor present exerts a pressure in proportion to its concentration, like other gases.)

As soon as air enters the respiratory tract, its composition changes (Table 33-1, Figure 33-25). Inspired air becomes saturated with water vapor as it travels through the air-filled passageways toward the alveoli. When inspired air reaches the alveoli, it mixes with residual air remaining from the previous respiratory cycle. Partial pressure of oxygen drops and that of carbon dioxide rises. Upon expiration, air from the alveoli mixes with air in the dead space to produce still a different mixture (Table 33-1). Although no significant gas exchange takes place in the dead space, the air it contains is the first air to leave the body when expiration begins.

Because the partial pressure of oxygen in lung alveoli is greater (100 mm Hg) than it is in venous blood of lung capillaries (40 mm Hg), oxygen diffuses into the lung capillaries. In a similar manner carbon dioxide in blood of the lung capillaries has a higher concentration (46 mm Hg) than has this same gas in lung alveoli (40 mm Hg), so carbon dioxide diffuses from the blood into the alveoli.

In tissues respiratory gases also move along their concentration gradients (Figure 33-25). Partial pressure of oxygen in the blood (100 mm Hg) is greater than in the tissues (0 to 30 mm Hg), and partial pressure of carbon dioxide in tissues (45 to 68 mm Hg) is greater than that in blood (40 mm Hg). In each case gases diffuse from a location of higher concentration to one of lower concentration.

How Respiratory Gases Are Transported
In some invertebrates respiratory gases are simply carried, dissolved in body fluids. However, solubility of oxygen is so low in water that it is adequate only for animals with low rates of metabolism. For example, only approximately 1% of a human’s oxygen requirement can be transported in this way. Consequently in many invertebrates and in virtually all vertebrates, nearly all oxygen and a significant amount of carbon dioxide are transported by special colored proteins, or respiratory pigments, in the blood. In most animals (all vertebrates) these respiratory pigments are packaged into blood cells.

Because of the weight of water, hydrostatic pressure increases the equivalent of 1 atmosphere for every 10 m of depth in seawater, and the pressure of the air supplied to a diver must be increased correspondingly so that it can be drawn into the lungs.Under the increased pressure, additional air dissolves in the blood, the amount depending on depth and time at depth of a dive. If a diver ascends slowly, the gas comes out of solution imperceptibly and is breathed out from the lungs.However, if the ascent is too rapid, the air comes out of solution and forms bubbles in the blood and other tissues, a condition known as decompression sickness or the bends. The result is painful and, if severe, can cause paralysis or death.

Sickle cell anemia is an up-to-now incurable, inherited condition in which a single amino acid (glutamic acid) in normal hemoglobin (HbA) is replaced by a valine in sickle cell hemoglobin (HbS). The ability of HbS to carry oxygen is severely impaired, and erythrocytes tend to crumple during periods of oxygen stress (for example, during exercise). Capillaries become clogged with misshapen red cells; the affected area is very painful, and the tissue may die. About 1 in 10 black Americans carry the trait (heterozygous). Heterozygotes do not have sickle cell anemia and live normal lives, but if both parents are heterozygous, each of their offspring has a 25% chance of inheriting the disease.

The most widespread respiratory pigment in the animal kingdom is hemoglobin, a red, iron-containing protein present in all vertebrates and many invertebrates. Each molecule of hemoglobin is 5% heme, an ironcontaining compound giving the red color to blood, and 95% globin, a colorless protein. The heme portion of hemoglobin has a great affinity for oxygen; each gram of hemoglobin can carry a maximum of approximately 1.3 ml of oxygen. Because there are approximately 15 g of hemoglobin in each 100 ml of blood, fully oxygenated blood contains approximately 20 ml of oxygen per 100 ml. Of course, for hemoglobin to be of value to the body it must hold oxygen in a loose, reversible chemical combination so that it can be released to tissues. The actual amount of oxygen that combines with hemoglobin depends on the shape or conformation of the hemoglobin molecule, which is affected by several factors, including the concentration of oxygen itself. When the oxygen concentration is high, as it is in the capillaries of the lung alveoli, hemoglobin loads up with oxygen; in tissues where the prevailing oxygen partial pressure is low, hemoglobin releases its stored oxygen reserves (Figure 33-26).


Although hemoglobin is the only vertebrate respiratory pigment, several other respiratory pigments are known among invertebrates.Hemocyanin, a blue, coppercontaining protein, occurs in crustaceans and most molluscs. Among other pigments is chlorocruorin (klor-a-cru-o-rin), a greencolored, iron-containing pigment found in four families of polychaete tube worms. Its structure and oxygen-carrying capacity are very similar to those of hemoglobin, but it is carried free in the plasma rather than being enclosed in blood corpuscles. Hemerythrin is a red pigment found in some polychaete worms. Although it contains iron, this metal is not present in a heme group (despite the name of the pigment!), and its oxygen-carrying capacity is poor compared to hemoglobin.

Unfortunately for humans and many other animals, hemoglobin has an affinity for carbon monoxide that is about 200 times greater than its affinity for oxygen. Consequently, even when carbon monoxide is present in the atmosphere at lower concentrations than oxygen, it tends to displace oxygen from hemoglobin to form a stable compound called carboxyhemoglobin.Air containing only 0.2% carbon monoxide may be fatal. Because of their higher respiratory rate, children and small animals are poisoned more rapidly than adults. Carbon monoxide is becoming an atmospheric contaminant of ever-increasing proportions as the world’s population and industrialization continue to increase rapidly.

We can express the relationship of carrying capacity to surrounding oxygen concentration as hemoglobin saturation curves (also called oxygen dissociation curves [Figure 33- 26]). As these curves show, the lower the surrounding oxygen tension, the greater the quantity of oxygen released. This important characteristic of hemoglobin allows more oxygen to be released to those tissues which need it most (those having the lowest partial pressure of oxygen).

Another factor that affects conformation of hemoglobin and therefore its release of oxygen to tissues is the sensitivity of oxyhemoglobin (hemoglobin with bound oxygen) to carbon dioxide. Carbon dioxide shifts the hemoglobin saturation curve to the right (Figure 33-26B), a phenomenon called the Bohr effect after the Danish scientist who first described it. As carbon dioxide enters the blood from respiring tissues, it causes hemoglobin to unload more oxygen. The opposite event occurs in the lungs; as carbon dioxide diffuses from venous blood into alveolar space, the hemoglobin saturation curve shifts back to the left, allowing more oxygen to be loaded onto hemoglobin.

The same blood that transports oxygen to the tissues from the lungs must carry carbon dioxide back to the lungs on its return trip. However, unlike oxygen that is transported almost exclusively in combination with hemoglobin, carbon dioxide is transported in three different forms. A small fraction of the blood-borne carbon dioxide, only about 7%, is carried as gas physically dissolved in the plasma. The remainder diffuses into red blood cells. In red blood cells, most carbon dioxide, approximately 70%, becomes carbonic acid through action of the enzyme carbonic anhydrase. Carbonic acid immediately dissociates into hydrogen ion and bicarbonate ion. We can summarize the entire reaction as follows:

Several systems buffer the hydrogenion concentration in blood, thus preventing a severe decrease in blood pH. Bicarbonate ions remain in solution in plasma and red blood cells since, unlike carbon dioxide, bicarbonate is extremely soluble (Figure 33-27).

Another fraction of the carbon dioxide, approximately 23%, combines reversibly with hemoglobin. Carbon dioxide does not combine with the heme group but with amino groups of several amino acids to form a compound called carbaminohemoglobin.

All of these reactions are reversible. When the venous blood reaches the lungs, carbon dioxide diffuses from red blood cells into alveolar air.