Breathing and Exchange of Gases

Every living cell needs oxygen (O₂) to break down food molecules and release the energy stored in them, and every living cell produces carbon dioxide (CO₂) that must be thrown out. The process of taking in oxygen from the surroundings and giving out the carbon dioxide produced by the cells is called breathing. Keep this separate from cellular respiration, which is the chemical breakdown of food that happens inside the cells. Breathing only moves the gases in and out; cellular respiration is the step that actually uses the oxygen and produces the carbon dioxide.

Different animals do this job with very different equipment, and the equipment depends on where the animal lives and how thick its body is. Simple animals such as sponges, coelenterates like Hydra, and flatworms have thin bodies in which no cell is far from the outside, so gases simply move in and out across the general body surface by diffusion. Earthworms use their moist cuticle. The moisture is not a detail you can skip: gases have to dissolve in a film of water before they can cross a living membrane, which is also why a dry respiratory surface stops working.

Insects follow a completely different design. They have a branching network of air tubes called the tracheal system that opens to the outside through small pores and carries air directly to the tissues. Because air reaches the cells through tubes, insect blood plays very little part in carrying oxygen, unlike in vertebrates where the blood is the main carrier.

Aquatic animals such as most fishes and aquatic arthropods use gills, and this is called branchial respiration. Gills are thin, highly folded outgrowths packed with blood vessels, and water supports them so that their delicate folds stay separated. On land the same structure would collapse and dry within minutes, so terrestrial animals use lungs, which is called pulmonary respiration. Lungs are internal, so they stay moist and protected. Amphibians such as the frog can use their moist skin as well, which is called cutaneous respiration, in addition to their lungs.

Run your eye across all these examples and the same three features keep coming back. A respiratory surface is thin, so gases have a short distance to travel; it is moist, so gases can dissolve; and it is richly supplied with blood, so the gas that has crossed is carried away and a steep gradient is maintained. The insect tracheal system is the one arrangement here that does without the blood supply, because it delivers air to the tissue itself.

The human respiratory system is one continuous passage, and it is far easier to learn as an ordered list of names than as a picture. Air enters through the external nostrils, which open above the upper lips, into the nasal chamber through the nasal passage. The nasal chamber opens into the nasopharynx, a part of the pharynx, which is the common passage for both food and air. The nasopharynx opens through the glottis, the opening of the wind pipe, into the trachea. The glottis lies in the larynx, a cartilaginous box that helps in producing sound and is therefore called the sound box. During swallowing, a thin elastic flap called the epiglottis covers the glottis so that the food is guided into the food pipe and does not enter the wind pipe.

The trachea is a straight tube that runs down into the middle of the thoracic cavity and divides at the level of the fifth thoracic vertebra into a right and a left primary bronchus. Each primary bronchus enters its own lung and branches again and again, giving secondary and tertiary bronchi, then finer and finer bronchioles, and finally the smallest terminal bronchioles. The trachea and the larger bronchi are held open by incomplete cartilaginous rings. The rings are shaped like the letter C and the gap in them faces the food pipe behind, which is why the airway can never collapse but a swallowed lump of food can still push the food pipe outward as it passes.

Each terminal bronchiole opens into a bunch of very thin-walled, balloon-like sacs called alveoli. This gives the system a clean two-part division. The conducting part stretches from the external nostrils up to the terminal bronchioles. Its job is to transport the air to the alveoli, to clear it of foreign particles, to humidify it and to bring it to body temperature. No gas exchange happens anywhere in the conducting part. The respiratory part, also called the exchange part, is made of the alveoli and their ducts, and this is the only region where O₂ and CO₂ actually diffuse between air and blood.

The lungs themselves sit inside an air-tight thoracic chamber, and it helps to learn its boundaries as directions rather than as a drawing. The vertebral column forms the boundary at the back (dorsally), the sternum forms it in front (ventrally), the ribs form it on the two sides (laterally), and the dome-shaped diaphragm, a sheet of muscle, forms it below. Each lung is covered by a double-layered pleura with pleural fluid in the space between the two layers. The outer pleural membrane is in close contact with the thoracic lining, and the inner pleural membrane is in contact with the lung surface. The pleural fluid reduces friction as the lungs slide against the chest wall with each breath.

One consequence of this arrangement carries the entire next section. Because the thoracic chamber is closed and air-tight and the two pleural layers stay stuck together through the fluid between them, any change in the volume of the thoracic chamber is passed on almost exactly to the lungs. Enlarge the chest and the lungs enlarge with it; shrink the chest and the lungs shrink. That single fact is the whole basis of the mechanism of breathing.

Breathing has two phases. Inspiration is the phase in which atmospheric air is drawn into the lungs, and expiration is the phase in which alveolar air is released out. Both are driven by one simple physical rule: air always moves from a region of higher pressure to a region of lower pressure. Applied to the lungs, this means inspiration can happen only when the pressure inside the lungs, called the intra-pulmonary pressure, is less than the atmospheric pressure, and expiration can happen only when the intra-pulmonary pressure is more than the atmospheric pressure. Everything else in this section is about how the body produces those two pressure states on demand.

To make the pressure inside the lungs fall, the body has to enlarge the thoracic chamber, and two muscle groups do it together. The diaphragm is dome-shaped and bulges upward into the chest when it is relaxed. When it contracts, it flattens, pushing the floor of the chest downward. This increases the volume of the thoracic chamber in the antero-posterior axis. At the same time the external inter-costal muscles, which lie between the ribs, contract and lift the ribs and the sternum upward and outward. This increases the volume of the thoracic chamber in the dorso-ventral axis. These two labels are easy to swap, so pair them deliberately and keep the pairs apart: diaphragm with antero-posterior, external inter-costal muscles with dorso-ventral. What each muscle group does is the part to hold on to: the diaphragm drops the floor of the chest, and the inter-costals swing the ribs and sternum up and out.

The increase in the volume of the thoracic chamber produces a matching increase in the pulmonary volume, because the chamber is air-tight and the pleural layers keep the lung surface following the chest wall. Once the lung volume goes up, the intra-pulmonary pressure falls slightly below the atmospheric pressure. A fall of about 1 mm Hg is enough to make air rush in from outside through the airway. That inrush is inspiration.

Quiet, normal expiration is passive. No muscle has to squeeze the chest inward. The diaphragm and the external inter-costal muscles simply relax. The diaphragm springs back into its dome shape, the ribs and sternum drop back to their resting position, the thoracic volume falls, the pulmonary volume falls with it, and the intra-pulmonary pressure rises slightly above the atmospheric pressure so that the air is forced out of the lungs. When you need a deeper or more forceful breath, additional muscles of the abdomen can be brought in, and these increase the strength of both inspiration and expiration. That is what happens when you blow out a candle hard or take a very deep breath before diving.

On an average, a healthy human being breathes about 12 to 16 times per minute. It is worth remembering that breathing is only the first of the five steps that make up respiration as a whole. The five are: (i) breathing or pulmonary ventilation, in which atmospheric air is drawn in and alveolar air is released out; (ii) diffusion of O₂ and CO₂ across the alveolar membrane; (iii) transport of the gases by the blood; (iv) diffusion of O₂ and CO₂ between the blood and the tissues; and (v) use of O₂ by the cells for catabolic reactions, with the resulting release of CO₂. So the word respiration covers all five of these steps, while breathing covers only the first.

The volume of air moved in and out of the lungs can be measured with an instrument called a spirometer, and these readings are used clinically to judge how well someone's lungs are working. The whole topic becomes easy once you separate the four volumes, which never overlap with one another, from the capacities, each of which is simply two or more volumes added together. If you can state the four volumes, you can derive every capacity on the spot without memorising them separately.

Tidal volume (TV) is the volume of air inspired or expired during a single normal breath, and it is approximately 500 mL. Multiply that by a resting breathing rate and you get roughly 6000 to 8000 mL of air moved every minute just by quiet breathing. Inspiratory reserve volume (IRV) is the additional volume of air a person can breathe in by a forcible inspiration, over and above a normal breath, and it is about 2500 to 3000 mL. Expiratory reserve volume (ERV) is the additional volume of air a person can breathe out by a forcible expiration, and it is about 1000 to 1100 mL. Residual volume (RV) is the volume of air that still remains in the lungs even after the most forcible expiration, and it is about 1100 to 1200 mL. Because of the residual volume, the lungs are never completely emptied, and gas exchange can continue in the gaps between breaths.

Now the capacities, each defined by a sentence you should be able to reproduce. Inspiratory capacity (IC) is the total volume of air a person can inspire after a normal expiration, and it equals TV + IRV. Expiratory capacity (EC) is the total volume of air a person can expire after a normal inspiration, and it equals TV + ERV. Functional residual capacity (FRC) is the volume of air that will remain in the lungs after a normal expiration, and it equals ERV + RV. Vital capacity (VC) is the maximum volume of air a person can breathe out after a forced inspiration, which is the same as the maximum volume a person can breathe in after a forced expiration, and it equals IRV + TV + ERV. Total lung capacity (TLC) is the total volume of air the lungs can hold at the end of a forced inspiration, and it equals RV + ERV + TV + IRV, which is the same thing as VC + RV.

Two points here are easy to get wrong. The first is the difference between vital capacity and total lung capacity: vital capacity does not include the residual volume, while total lung capacity does. That is the only difference between them, and it is also why vital capacity can be measured directly by blowing into a spirometer while total lung capacity cannot. The second is functional residual capacity: it is what remains after a normal quiet expiration, not after a forced one. After a forced expiration, only the residual volume is left behind. Learning these as full sentences, with the words normal and forced included, is far more reliable than trying to recall a stack of numbers under exam pressure.

A quick worked check: if TV is 500 mL, IRV is 3000 mL, ERV is 1100 mL and RV is 1200 mL, then IC is 3500 mL, EC is 1600 mL, FRC is 2300 mL, VC is 4600 mL and TLC is 5800 mL. Notice that TLC minus VC gives back RV, which is a handy way to check your own arithmetic.

Gas exchange happens at two places in the body: at the alveoli, between the alveolar air and the blood, and at the tissues, between the blood and the body cells. Both are pure diffusion. No energy is spent, no pump is involved, and the direction of movement is decided entirely by the partial pressure of the gas concerned. Partial pressure is the pressure contributed by an individual gas in a mixture of gases; it is written pO₂ for oxygen and pCO₂ for carbon dioxide and is measured in mm Hg. Each gas moves independently, from wherever its own partial pressure is higher to wherever it is lower.

Take oxygen first, and follow the numbers as a chain. In atmospheric air pO₂ is about 159 mm Hg. In the alveoli it has dropped to about 104 mm Hg, because alveolar air is a mixture of fresh air and air that was already there. In the deoxygenated blood that arrives at the alveolar capillaries, pO₂ is only about 40 mm Hg. Oxygen therefore diffuses from the alveoli into the blood, and the oxygenated blood leaving the alveoli has a pO₂ of about 95 mm Hg. At the tissues, pO₂ is again about 40 mm Hg, because the cells are constantly consuming oxygen, so oxygen now diffuses from the blood into the tissues.

For carbon dioxide every gradient runs the opposite way. In the tissues and in the deoxygenated blood, pCO₂ is about 45 mm Hg. In the alveoli and in the oxygenated blood it is about 40 mm Hg. In atmospheric air it is only about 0.3 mm Hg. So carbon dioxide diffuses from the tissues into the blood, then from the blood into the alveoli, and finally out into the atmosphere with each expiration.

Something in those numbers should look odd. The carbon dioxide gradient at the alveoli is only 45 to 40 mm Hg, a difference of about 5 mm Hg, while the oxygen gradient there is 104 to 40 mm Hg, a difference of about 64 mm Hg. How does carbon dioxide leave efficiently across such a small gradient? The answer is solubility. The solubility of CO₂ is roughly 20 to 25 times higher than that of O₂, so the amount of CO₂ that can diffuse through the membrane per unit difference in partial pressure is far greater. Diffusion depends on solubility as well as on the size of the gradient, so a small gradient for a highly soluble gas can still shift a large quantity of that gas.

The barrier the gases cross is called the diffusion membrane, and it is built from three layers. The three are the thin squamous epithelium of the alveoli, which faces the air; the endothelium of the alveolar capillaries, which faces the blood; and the basement substance, which lies in between those two. So an oxygen molecule travelling from alveolar air into the blood crosses the alveolar epithelium first, then the basement substance, then the capillary endothelium. The total thickness of all three together is much less than a millimetre, which is exactly why diffusion across it is so quick. The factors that favour rapid exchange here are therefore the thinness of this membrane, the very large total surface area offered by the alveoli, the steep partial pressure gradients, and the high solubility of the gases. Any disease that thickens this membrane or destroys alveolar surface will slow exchange down, even when breathing movements look completely normal from the outside.

Blood is the medium that carries both gases around the body, but it does not carry them in the same way, and the two sets of percentages must not be mixed up. For oxygen, about 97 per cent is transported by the red blood cells and the remaining 3 per cent is carried in a dissolved state in the plasma. For carbon dioxide, about 20 to 25 per cent is carried by the red blood cells as carbamino-haemoglobin, about 70 per cent travels as bicarbonate ions, and about 7 per cent is carried dissolved in the plasma. Notice that the dissolved fraction is larger for carbon dioxide (7 per cent) than for oxygen (3 per cent), which follows directly from carbon dioxide being far more soluble.

Oxygen binds to haemoglobin, the red, iron-containing pigment present in the red blood cells, and the product is called oxyhaemoglobin. One molecule of haemoglobin can carry a maximum of four molecules of oxygen. The binding is reversible, which is the whole point: it must form easily in the lungs and come apart easily in the tissues. How much binding occurs is decided primarily by pO₂, while pCO₂, hydrogen ion concentration and temperature are the other factors that can interfere with it.

If you plot the percentage saturation of haemoglobin with oxygen on the vertical axis against pO₂ on the horizontal axis, you get the oxygen dissociation curve, and it is sigmoid, that is, S-shaped, not a straight line. You can read its usefulness straight from its shape without seeing the graph. Over the high pO₂ range found in the alveoli the curve is almost flat and close to full saturation, so haemoglobin loads up completely and small dips in alveolar pO₂ hardly matter. Over the lower pO₂ range found in the tissues the curve is steep, so even a small fall in pO₂ makes haemoglobin release a large quantity of oxygen exactly where it is needed.

In the alveoli, pO₂ is high, pCO₂ is low, hydrogen ion concentration is low and the temperature is lower. Every one of those four conditions favours the formation of oxyhaemoglobin. In the tissues, pO₂ is low, pCO₂ is high, hydrogen ion concentration is high and the temperature is higher, and every one of those four favours the dissociation of oxygen from oxyhaemoglobin. This shift of the curve to the right, caused by more carbon dioxide, more hydrogen ions (that is, a lower pH) and a higher temperature, is commonly known as the Bohr effect. It is a neat piece of design: the harder a tissue is working, the more carbon dioxide, acid and heat it makes, and the more oxygen it is handed. Under normal physiological conditions, every 100 mL of oxygenated blood delivers around 5 mL of O₂ to the tissues.

Carbon dioxide is handled by two separate chemistries. The first is direct binding to haemoglobin to form carbamino-haemoglobin. This binding is related to the partial pressure of CO₂, and pO₂ is a major interfering factor. Where pCO₂ is high and pO₂ is low, as in the tissues, more binding takes place. Where pCO₂ is low and pO₂ is high, as in the alveoli, carbamino-haemoglobin dissociates and the carbon dioxide is set free.

The second route carries the bulk of the load. Red blood cells contain a very high concentration of the enzyme carbonic anhydrase, and the plasma contains only minute quantities of it. This enzyme speeds up the following reaction in both directions: CO₂ + H₂O in the presence of carbonic anhydrase gives H₂CO₃, which in turn gives HCO₃^- + H⁺. At the tissue site, where pCO₂ is high because of ongoing catabolism, carbon dioxide diffuses into the blood and is converted into bicarbonate ions and hydrogen ions. At the alveolar site, where pCO₂ is low, the very same reaction is driven in the reverse direction: bicarbonate and hydrogen ions recombine to give carbonic acid, which yields carbon dioxide and water, and the carbon dioxide is released into the alveoli. In other words, the carbon dioxide trapped as bicarbonate at the tissue level is carried to the alveoli and set free there as a gas. Every 100 mL of deoxygenated blood delivers approximately 4 mL of CO₂ to the alveoli.

You do not have to think about breathing, and yet the rate and depth of your breathing change the moment you climb a staircase. That adjustment is made by the nervous system, and the human body has a specialised mechanism for it that keeps the concentrations of the respiratory gases within a narrow range.

The respiratory rhythm centre is present in the medulla region of the brain, and it is primarily responsible for the regulation of respiration. A second centre, the pneumotaxic centre, is present in the pons region of the brain, and it can moderate the functions of the respiratory rhythm centre. Neural signals from the pneumotaxic centre can reduce the duration of inspiration and thereby alter the respiratory rate. Keep the two apart by their locations and their jobs: the medulla sets the basic rhythm, the pons fine-tunes it.

Alongside the rhythm centre there is a chemosensitive area that is highly sensitive to carbon dioxide and hydrogen ions. When the levels of these substances rise, this area is activated and it sends signals to the rhythm centre to make the necessary adjustments, mainly by stepping up breathing so that the extra carbon dioxide is eliminated. In addition, receptors associated with the aortic arch and the carotid artery also recognise changes in carbon dioxide and hydrogen ion concentration and send the necessary signals to the rhythm centre for remedial action.

One point here is easy to state backwards, so learn it deliberately: the role of oxygen in the regulation of respiratory rhythm is quite insignificant. It is the build-up of carbon dioxide and hydrogen ions, not a shortage of oxygen, that is the main chemical signal to breathe harder. This is why you feel the urge to breathe after holding your breath long before your body has actually run short of oxygen.

A few disorders of the respiratory system are studied along with all this, and they are described here simply as facts about what goes wrong inside the lungs.

Asthma is difficulty in breathing, causing wheezing, due to inflammation of the bronchi and bronchioles. Because the inflamed airways are narrowed, moving air in and out becomes hard work, which produces the whistling sound.

Emphysema is a chronic disorder in which the alveolar walls are damaged, so that the respiratory surface available for gas exchange is reduced. One of the major causes is cigarette smoking. Reading this next to the diffusion membrane makes the breathlessness easy to understand: the lungs may still fill with air, but there is far less surface across which that air can exchange gases with the blood.

Occupational respiratory disorders occur in certain industries, especially those that involve grinding or stone-breaking, where so much dust is produced that the defence mechanism of the body cannot fully cope with the situation. Long exposure can give rise to inflammation leading to fibrosis, which is the proliferation of fibrous tissue, and this causes serious lung damage. Silicosis, from long exposure to silica dust, and asbestosis, from asbestos fibres, are named examples of this kind of damage. Workers in such industries should wear protective masks.