Gas exchange in mammals: lungs and ventilation

From trachea to alveolus, and what changes on the way

Air entering the nose is warmed, moistened and filtered, then passes down the trachea, a tube about 10 cm long held permanently open by rings of cartilage. The rings are C-shaped rather than complete, with the gap at the back where the oesophagus lies against the trachea, so a swallowed mouthful can bulge into that space instead of being crushed against a rigid tube.

The trachea divides into two bronchi, one to each lung, and each bronchus divides again and again into bronchioles of decreasing diameter. Around twenty-three rounds of branching separate the trachea from the smallest air spaces. The finest bronchioles open into clusters of alveoli, and that is where nearly all the gas exchange happens. Strictly, the last generations of bronchioles carry scattered alveoli in their own walls and exchange a little themselves; 'in the alveoli' remains the exam answer.

Describe the drawing

Four ring-shaped cross-sections drawn down the left of the figure. The trachea has one thick incomplete ring of cartilage with a lining of ciliated and goblet cells; the bronchus has four separate blocks of cartilage and the same lining; the bronchiole has a thick ring of smooth muscle and no cartilage; and the alveoli are three thin sacs lying against a capillary. A key beneath gives the colours for ciliated cells, goblet cells, cartilage and smooth muscle.

Cartilage

A firm, flexible supporting tissue. In the trachea it forms incomplete rings, and in the bronchi irregular blocks, holding the airway open against the pressure drop of inspiration.

Ciliated epithelium

An epithelium whose cells carry cilia that beat in a co-ordinated wave, sweeping mucus and trapped particles up towards the throat.

Goblet cell

A cell in the airway epithelium that secretes mucus, which traps dust, pollen and bacteria.

Smooth muscle

Involuntary muscle in the walls of hollow organs and vessels. In the airway wall its contraction narrows the lumen, and it is the tissue that contracts inappropriately during an asthma attack.

Elastic fibres

Fibres that stretch as the lungs inflate and recoil as the muscles relax, providing much of the force for quiet expiration.

Squamous epithelium

An epithelium of very flattened cells, giving a wall a fraction of a micrometre thick; the lining of an alveolus.

Cambridge International 9700 requires candidates to identify tissues in sections and micrographs of the gas-exchange system. Use cartilage distribution, smooth muscle and epithelial thickness to distinguish the trachea, bronchi, bronchioles and alveoli: rings of cartilage indicate trachea, irregular blocks of cartilage indicate bronchus, a conspicuous ring of smooth muscle without cartilage indicates bronchiole, and a single squamous layer against a capillary indicates alveolus. Beneath the epithelium of the trachea and bronchi lie mucous glands, which secrete mucus through ducts onto the lining; with the goblet cells, they supply the mucus that traps dust and pathogens for the cilia to sweep away.

Smooth muscle and elastic fibres are present along the length of the airway tree and act in opposition. Smooth muscle contracts to narrow an airway; elastic fibres stretch as it does and recoil to widen the airway when the muscle relaxes. Elastic fibres are not muscle, so they are not an antagonistic muscle pair.

The surface itself

Published estimates for an adult give of the order of 300 million alveoli and a combined surface area in the range of about 50 to 75 m², commonly quoted as roughly 70 m². Subdivision into alveoli provides that area within a thoracic cavity of a few litres, which raises the first term of Fick's law at little cost in volume.

Each alveolus is lined by a single layer of squamous epithelium and wrapped in a dense network of capillaries so narrow that red blood cells pass through in single file, squeezed against the capillary wall. Between the air and the haemoglobin lie only the alveolar epithelium, a basement membrane shared with the capillary, the capillary endothelium and a film of plasma.

Describe the drawing

At the top, a round alveolus on the left with an arrow for oxygen crossing to a capillary on the right that carries four red blood cells, and an arrow for carbon dioxide crossing back. Below, the same barrier drawn as four stacked bands: alveolar epithelium, shared basement membrane, capillary endothelium, and the plasma holding a red cell.

The difference in concentration is maintained on both sides, which is the second term of Fick's law. Each breath replaces part of the alveolar air with fresh air, so the oxygen partial pressure in the alveolus stays around 13.3 kPa. Blood arriving from the pulmonary artery has an oxygen partial pressure of about 5.3 kPa. Each red cell loads within the first third or so of its passage along the capillary and is then carried away, while fresh deoxygenated blood keeps arriving behind it, so the gradient across the surface as a whole is never used up. Carbon dioxide crosses the other way down a much smaller gradient, roughly 6.1 kPa in the arriving blood against 5.3 kPa in the alveolus, and that suffices because carbon dioxide diffuses far more readily than oxygen.

Two further features of the surface matter. The alveolar lining is kept moist, because a gas has to dissolve before it can diffuse across a membrane. And the fluid contains a surfactant secreted by specialised cells in the alveolar wall, which lowers surface tension and stops the smallest alveoli collapsing shut between breaths. Premature babies are often short of it, which is why respiratory distress syndrome is a risk of early birth.

Elastic fibres in the alveolar walls stretch during inspiration and store energy while they do. Releasing it is what drives quiet expiration. In emphysema those fibres are destroyed and the alveolar walls break down into fewer, larger spaces, so the surface area falls and the recoil weakens at the same time. Both changes reduce gas exchange, and an account of emphysema should name both.

Ventilation: muscles, then volume, then pressure, then air

Lung tissue contains no skeletal muscle. Airway smooth muscle changes airway resistance but does not ventilate the lungs, and the muscles that do are in the wall of the sealed cavity the lungs sit in: the diaphragm underneath and the intercostal muscles between the ribs.

What ties lung to wall is the pleura: one membrane on the lung's surface, one lining the cavity, and between them a thin film of fluid at slightly below atmospheric pressure. The film lets the lungs slide against the wall but not pull away from it, so when the cavity expands the lungs are carried with it.

Describe the drawing

Breathing animated in four steps. Between breaths the ribcage and the domed diaphragm are still and no air moves. Then the external intercostal muscles contract, the ribs swing upwards and outwards and the diaphragm contracts and flattens downwards, enlarging the chest. With the chest larger the pressure inside falls and an arrow shows air flowing down the trachea into the lungs. Finally the muscles relax, the ribcage drops, the diaphragm domes upward again and the arrow reverses as air leaves.

The external and internal intercostals are an antagonistic pair. Externals contract for inspiration, internals for forced expiration, and at any moment one set is relaxed. In quiet breathing the internals do essentially nothing, because recoil of the stretched elastic tissue and the weight of the ribcage are enough. They come into play when you blow out hard, along with the abdominal muscles, which push the abdominal contents up against the diaphragm.

State the asymmetry explicitly. Inspiration always requires energy, because it always involves muscle contraction. Quiet expiration is largely passive: the diaphragm does not push upwards or contract upwards, since a muscle can only pull, and it returns to its domed shape when it stops contracting.

The pressure changes involved are small. Between breaths the pressure in the alveoli equals atmospheric pressure exactly, so no air moves. During quiet inspiration it falls by only a fraction of a kilopascal, which is ample: gases move quickly down even a shallow pressure gradient. On a trace of alveolar pressure against time, air enters wherever the trace lies below the atmospheric line and leaves wherever it lies above it.

Putting numbers on it

AQA names one calculation of its own in this topic, and it is the volume of air moved per minute. OCR A reaches the same quantity through a spirometer trace.

pulmonary ventilation rate = tidal volume × ventilation rateAlso called minute ventilation. Tidal volume in dm³, ventilation rate in breaths per minute, so the answer is in dm³ min⁻¹.

Tidal volume

The volume of air moved in or out in one normal breath at rest, about 0.5 dm³ in an adult.

Ventilation rate

The number of breaths taken per minute, about 12 to 15 at rest. Also called breathing rate.

Vital capacity

The largest volume that can be breathed out after the deepest possible breath in; roughly 4.6 dm³ in a young adult man and 3.1 dm³ in a young adult woman.

Residual volume

The volume left in the lungs after the hardest possible breath out, about 1.2 dm³. It cannot be measured with a spirometer, because it never leaves the lungs. Vital capacity plus residual volume is the total lung capacity.

The ventilation centre in the medulla oblongata makes these changes. During exercise the muscles release more carbon dioxide, more carbonic acid forms and the pH of the blood falls. Chemoreceptors in the carotid and aortic bodies and in the medulla detect the fall and send more impulses to the ventilation centre, which sends impulses more often to the diaphragm and the external intercostal muscles. They contract more strongly and more often, so breathing becomes deeper and faster, carbon dioxide is removed faster and the pH returns towards normal.

A spirometer records the volume of air in a closed circuit against time, and OCR A expects lung volumes and oxygen uptake to be read from one. Oxygen uptake is measured using the soda lime in the circuit: it absorbs the carbon dioxide the subject breathes out, so the total volume of gas in the apparatus falls steadily by exactly the volume of oxygen consumed. Draw a line through the midpoints of the oscillations, take its gradient, and that gradient is the rate of oxygen uptake. Without the soda lime the exhaled carbon dioxide would roughly replace the oxygen removed and the trace would stay level.

One further quantity qualifies these figures. About 150 cm³ of each breath never reaches an alveolus; it stays in the airways from the nose to the bronchioles, which are conducting tubes with no exchange surface. That volume is the dead space. It means a shallow, rapid breathing pattern moves less useful air than a slow deep one at the same pulmonary ventilation rate, because the dead space is paid for on every breath.

Lung disease and what it does to the data

AQA 7401/7402 asks students to interpret information about the effects of lung disease on gas exchange and ventilation, and to read lung-function data. The other boards do not include lung disease in their gas exchange topic, although every board teaches tuberculosis elsewhere as an infectious disease.

Each disease reduces the rate of gas exchange by acting on a term of Fick's law, or on ventilation, which keeps the concentration gradient up. The data show two broad patterns. In an obstructive disease the airways are narrowed, so air cannot be moved in and out quickly. In a restrictive disease the lungs cannot expand fully, so less air can be moved at all.

A clinic spirometer test separates the two. The patient breathes in as deeply as possible, then breathes out as hard and as fast as possible until no more air will leave, and two volumes are read from the forced breath out.

Forced vital capacity (FVC)

The total volume of air breathed out in one forced breath after the deepest possible breath in. In healthy lungs it is close to the vital capacity.

Forced expiratory volume in one second (FEV₁)

The volume of air breathed out in the first second of a forced breath out. It falls when the airways are narrowed, because air cannot leave them quickly.

FEV₁ ÷ FVC ratio

The fraction of the forced vital capacity breathed out in the first second. In a healthy adult it is usually above 0.7, often around 0.8; a value below 0.7 is the threshold commonly used to indicate airway obstruction.

Obstructive lung disease

A disease that narrows the airways and raises the resistance to air flow, so FEV₁ falls more than FVC and the ratio drops. Asthma and emphysema are examples.

Restrictive lung disease

A disease that stops the lungs expanding fully, so FVC and FEV₁ fall together and the ratio stays normal or rises. Pulmonary fibrosis is an example.

Describe the drawing

A spirometer trace plotted as the volume of air in the lungs, in cubic decimetres, against time in seconds, with constructed values for a healthy young adult. For twelve seconds the line rises and falls between 2.4 and 2.9, three quiet breaths of 0.5 cubic decimetres. It then climbs to 6.2 with the deepest possible breath in, and at fifteen seconds falls steeply as the subject breathes out as hard and fast as possible: 4.0 cubic decimetres leave in the first second, marked as FEV1, and the line levels off at 1.2, so the forced vital capacity is 5.0. A dashed line at 1.2 marks the residual volume.

Read every quantity as a difference. Tidal volume is the height of one quiet breath, here 2.9 − 2.4 = 0.5 dm³, and ventilation rate is 60 divided by the time for one breath, here 60 ÷ 4 = 15 breaths per minute. FEV₁ is the fall in the first second after the forced breath begins, 6.2 − 2.2 = 4.0 dm³. FVC is the whole fall from the top of the deepest breath to the level at which the trace flattens, 6.2 − 1.2 = 5.0 dm³. So this subject breathes out 4.0 ÷ 5.0 = 0.80 of the forced vital capacity in the first second.

In asthma the lining of the airway reacts to something harmless. Mast cells in the lining release histamine and other chemicals, which cause inflammation, extra mucus and contraction of the bronchiole smooth muscle. In emphysema the damage starts with smoke: particles and tar inflame the alveoli, phagocytes gather there, and enzymes they release, such as elastase, digest the elastic fibres. Smoke also damages the cilia, so mucus and trapped particles are cleared more slowly.

Breathlessness in all four diseases has the same cause. Each breath delivers less oxygen to the blood and removes less carbon dioxide, so the ventilation centre raises the rate and depth of breathing. Where the lungs are stiff the depth cannot rise far, so the rate does, and because the dead space is paid on every breath, rapid shallow breathing delivers less air to the alveoli than its pulmonary ventilation rate suggests.

Describe the drawing

Three curves of volume breathed out against time over eight seconds of a forced breath out, with constructed values and a dashed line at one second. The healthy curve rises steeply to 4.0 cubic decimetres at one second and levels off at 5.0. The curve for stiff, scarred lungs rises almost as steeply but levels off early, at 2.4 by one second and 2.8 in all. The curve for narrowed airways rises slowly, reaching only 1.6 at one second and creeping up to about 3.6.

Risk factors, evidence and the law

A risk factor is anything that raises the probability of developing a disease. For lung disease the main ones are smoking; air pollution, particularly the fine particles from traffic and burning fuel; dust and fibres breathed in at work, such as coal dust, silica and asbestos; and genetic make-up. AQA expects students to interpret data linking these factors to the incidence of lung disease, to recognise correlations and causal relationships, and to evaluate the way experimental data led to statutory restrictions on the sources of risk.

Risk factor

Anything that increases the probability that a person will develop a disease, such as smoking for lung cancer and emphysema.

Incidence

The number of new cases of a disease in a population over a stated period, usually given per 100 000 people per year so that populations of different sizes can be compared.

A correlation shows only that two variables change together. A third variable may drive both: if the smokers in a sample were also more likely to work in dusty jobs, part of the link between smoking and lung disease could come from the dust. Evidence for a causal link builds up when several kinds of finding agree, and the case against smoking is the standard example.

Evidence that smokers harm themselves justified health warnings, taxes and limits on advertising. A ban on smoking in public places rests on a different claim: that smoke harms people who have not chosen to breathe it. That evidence came from studies of non-smokers exposed to other people's smoke, such as the non-smoking wives of smokers. In 1998 the Scientific Committee on Tobacco and Health, which advised the UK government, concluded that long-term exposure to other people's smoke raises a non-smoker's risk of lung cancer by roughly 20 to 30 per cent.

Bar and restaurant staff could not avoid the smoke at work, and protecting them was the main argument for the laws that followed. Smoking in enclosed public places and workplaces was banned in Scotland in March 2006, in Wales and Northern Ireland in April 2007 and in England in July 2007.

Other risk factors have followed the same route from data to law. The London smog of December 1952, after which about 4,000 more people died in the following weeks than would otherwise have been expected, mostly from heart and lung disease, led to the Clean Air Act 1956 and its smoke control areas. Evidence that asbestos fibres cause asbestosis, a form of pulmonary fibrosis, and cancers of the lung and pleura led the UK to ban the import and use of blue and brown asbestos in 1985 and of white asbestos, the last type still in use, in 1999.

To evaluate how data led to a restriction, weigh both sides. In favour of the conclusion: very large samples, consistent results across many studies and countries, a dose-response relationship, the correct time order, a fall in risk when the exposure stops, and a plausible mechanism. Against it: almost all the data are correlational, because nobody can be assigned at random to smoke or to breathe asbestos; smoking is usually self-reported; and confounding variables can be reduced by matching or statistical adjustment but never removed.

Data collected after a law need the same care. A fall in disease supports the law only if the trend beforehand is taken into account, since rates may already have been falling. Hospital admissions for childhood asthma in Scotland, for instance, had been rising before the 2006 law and fell after it.