The gas exchange system

Mammals are endothermic (warm-blooded) and active, so their cells respire aerobically at high rates and need a continuous supply of O₂ and removal of CO₂. However, because mammals are large multicellular organisms, their surface area-to-volume (SA:V) ratio is too small for the body surface alone to supply enough oxygen by diffusion — only a thin film of cells near the surface could be served.

The mammalian solution is a specialised internal gas exchange system — the lungs — together with a transport system (blood, heart, vessels) that distributes the dissolved gases to and from every body cell.

A good gas exchange surface must have:

• a large surface area (Fick's law: rate ∝ surface area);
• a short diffusion distance (rate ∝ 1/distance);
• a steep concentration gradient (rate ∝ concentration difference);
• a moist surface (gases must dissolve to diffuse across cell membranes).

The alveolar surface meets all four. Ventilation (breathing) and blood circulation work together to maintain steep gradients.

Air passes from the mouth/nose into the pharynx, then through the larynx into the trachea. The trachea bifurcates into two main bronchi (one to each lung), which divide repeatedly into smaller bronchi, bronchioles, terminal bronchioles and finally the alveolar ducts that lead into the alveoli.

Each layer of the airway has a different composition reflecting its function:

Structure	Cartilage	Epithelium	Goblet cells	Smooth muscle	Elastic fibres
Trachea	C-shaped rings	Ciliated columnar	Many	Yes (small band)	Yes
Bronchus	Irregular plates	Ciliated columnar	Many	Yes (more)	Yes
Bronchiole	NONE	Ciliated cuboidal → simple	Few → none	Yes (proportionally most)	Yes
Alveolus	None	Squamous (single cell)	None	None	Yes (in wall)

Cartilage keeps the airway open against the negative pressures generated during inspiration. The trachea has C-shaped rings (open at the back) to allow the oesophagus to bulge during swallowing; bronchi have smaller, irregular plates; bronchioles have none, which is why bronchospasm can constrict them in asthma.

Ciliated columnar epithelium sweeps a layer of mucus upwards, away from the alveoli, towards the pharynx where it is swallowed (the mucociliary escalator).

Goblet cells (and submucosal mucous glands) secrete mucus that traps dust, bacteria and other particles. They are abundant in the trachea and bronchi but disappear in the smaller bronchioles.

Smooth muscle allows the airways to constrict (bronchoconstriction) or relax (bronchodilation), altering airflow. It is proportionally most important in the bronchioles, where there is no cartilage.

Elastic fibres in the airway walls and in the alveolar walls stretch on inspiration and recoil on expiration, helping to expel air passively.

Each lung contains approximately 300 million alveoli, giving a combined surface area of about 70 m² in an adult — roughly the floor area of a small classroom. This is the largest of all the adaptations for efficient gas exchange.

The alveolar wall is a single layer of squamous epithelial cells (type I pneumocytes), about 0.1 μm thick. The capillary endothelium that lies against it is also a single cell thick. The total diffusion distance between alveolar air and red blood cell is therefore only about 0.5 μm.

Each alveolus is surrounded by a dense network of pulmonary capillaries. These capillaries are slightly narrower than red blood cells, so RBCs are forced into single file. This (a) slows their passage so there is more time for exchange, and (b) brings haemoglobin into very close contact with the alveolar wall.

Ventilation (breathing) continuously replaces alveolar air with fresh O₂-rich air and removes CO₂-rich air, while blood flow continuously delivers O₂-poor blood and removes O₂-loaded blood. Both flows maintain steep concentration gradients for both gases.

The alveolar surface is kept moist by a thin layer of fluid: gases must dissolve before they can diffuse across cell membranes. This fluid contains surfactant (a phospholipid-protein mixture secreted by type II pneumocytes) that lowers surface tension and prevents alveolar collapse on expiration.

Finally, elastin fibres in the alveolar wall stretch on inspiration and recoil on expiration, helping push air out and maintaining ventilation efficiency.

Breathing (ventilation) is the result of pressure changes in a sealed thoracic cavity. By Boyle's law, at constant temperature the pressure of a gas is inversely proportional to its volume ($PV = \text{constant}$). Increasing the volume of the thorax therefore lowers the pressure inside the lungs, and air flows in from the higher-pressure atmosphere.

Inspiration (active)

1. The diaphragm (a dome-shaped sheet of skeletal muscle) contracts and flattens, moving downwards.
2. The external intercostal muscles contract, pulling the ribs upwards and outwards (the 'bucket-handle' and 'pump-handle' movements).
3. Both movements increase the volume of the thorax.
4. Intrapulmonary pressure falls below atmospheric pressure.
5. Air flows down the pressure gradient through the trachea and bronchi into the alveoli; the lungs inflate.

Expiration (passive at rest)

1. The diaphragm and external intercostals relax; the diaphragm domes upwards and the ribs drop down and in.
2. The thoracic volume decreases.
3. Elastic recoil of the lungs (alveolar elastin) and the ribcage helps to push the volume back down.
4. Intrapulmonary pressure rises above atmospheric pressure.
5. Air flows out down the pressure gradient.

Forced expiration (e.g. during exercise, coughing or playing a wind instrument) is active: the internal intercostals contract to pull ribs down and in, and the abdominal muscles push the diaphragm upwards.

Lung volumes can be measured using a spirometer. The key terms are:

• Tidal volume (TV) — the volume moved in/out of the lungs in one normal breath. At rest: ~0.5 dm³ (500 cm³).
• Inspiratory reserve volume (IRV) — extra air that can be inhaled beyond a normal tidal inhalation. ~3.0 dm³.
• Expiratory reserve volume (ERV) — extra air that can be forcibly exhaled beyond a normal tidal exhalation. ~1.1 dm³.
• Residual volume (RV) — air that cannot be expelled even after maximum exhalation. ~1.2 dm³. The residual volume keeps alveoli partly inflated so they don't collapse and ensures continuous gas exchange between breaths.
• Vital capacity (VC) = TV + IRV + ERV ≈ 4-5 dm³ in a healthy adult. Vital capacity is the maximum volume that can be exhaled after the deepest inhalation.
• Total lung capacity (TLC) = VC + RV ≈ 5-6 dm³.

Vital capacity falls in smokers and people with emphysema (loss of elastic recoil; air trapped → increased residual volume, decreased VC) and in restrictive lung diseases (e.g. fibrosis).

Ventilation rate = tidal volume × breathing frequency (breaths per minute). At rest in an adult: ~0.5 dm³ × 12 breaths min⁻¹ ≈ 6 dm³ min⁻¹. During exercise this can rise above 100 dm³ min⁻¹ as both TV and frequency increase.

Cigarette smoke contains over 4 000 chemicals. The most damaging are:

• Tar — a sticky brown residue containing many carcinogens (e.g. benzpyrene, nitrosamines).
• Nicotine — addictive; raises heart rate and blood pressure (CVD risk).
• Carbon monoxide — binds irreversibly to haemoglobin (forming carboxyhaemoglobin), reducing the oxygen-carrying capacity of blood.
• Irritants — paralyse cilia and stimulate mucus production.

Chronic bronchitis. Cigarette smoke paralyses and destroys the cilia lining the airways, while simultaneously stimulating goblet cells and mucous glands to over-produce mucus. With the mucociliary escalator disabled, thick mucus accumulates in the bronchi and bronchioles, narrowing them and providing a culture ground for bacterial infections. The bronchi become chronically inflamed. Symptoms: persistent productive 'smoker's cough', breathlessness, frequent chest infections.

Emphysema. Smoke attracts phagocytes (macrophages and neutrophils) to the alveolar walls. These phagocytes release the proteolytic enzyme elastase, which hydrolyses elastin in the alveolar walls. The walls between neighbouring alveoli break down, merging them into fewer, larger air sacs. Consequences:

• Reduced surface area for gas exchange → low blood O₂ saturation → breathlessness.
• Loss of elastic recoil → air is trapped in the lungs → increased residual volume, decreased vital capacity.

Patients become severely breathless on minimal exertion and the chest may become 'barrel-shaped'. Emphysema is irreversible.

Lung cancer. Carcinogens in tar enter epithelial cells in the bronchi (or sometimes alveoli) and damage DNA, causing mutations in proto-oncogenes (e.g. KRAS) and tumour-suppressor genes (e.g. TP53). Mutated cells divide uncontrollably to form a malignant tumour, which may metastasise via the blood or lymph to other organs (liver, brain, bones). Lung cancer is the leading smoking-related cause of death.

Smoking also increases the risk of cardiovascular disease (atherosclerosis, coronary heart disease, stroke) through CO, nicotine and endothelial damage — covered in the next topic on circulation.

Cambridge 9700 Paper 2 and Paper 4 frequently show light or electron micrographs of airway sections. You should be able to recognise:

• Trachea / bronchus: tall ciliated columnar epithelium with rows of cilia at the apical surface; goblet cells appear as pale, mucus-filled, cup-shaped cells between the columnar cells; below the epithelium is connective tissue (with mucous glands); then smooth muscle; then cartilage (which stains a distinctive pale blue/purple); the lumen is the central airway.
• Bronchiole: simpler columnar or cuboidal epithelium; few or no goblet cells; no cartilage; relatively thick smooth muscle layer in proportion to the airway diameter.
• Alveolus: thin sac-like spaces in the lung tissue, bordered by very thin squamous epithelium; capillaries can be seen between alveoli; type I pneumocytes are flat and form the wall; type II pneumocytes are cuboidal and secrete surfactant; alveolar macrophages ('dust cells') may be visible inside the alveolar lumen.

Practise drawing labelled diagrams. The most common labels Cambridge expects: cartilage, ciliated epithelium, goblet cell, smooth muscle, elastic fibres, lumen, alveolus, capillary, squamous epithelium.