Respiratory Physiology

Every cell in the body needs a continuous supply of oxygen (O₂) to produce energy, and continuously generates carbon dioxide (CO₂) as a waste product of that energy production. The lungs exist to solve one problem: how to efficiently exchange O₂ and CO₂ between the air and the blood, every second of every day. The respiratory system has two jobs: 1. Ventilation — moving air in and out of the lungs (breathing) 2. Gas exchange — transferring O₂ from air into blood, and CO₂ from blood into air These sound similar but are physiologically distinct. A patient can be breathing (ventilating) but not exchanging gases effectively — this is what happens in pneumonia, where alveoli fill with fluid. The journey of a breath: Air enters through the nose or mouth → travels down the trachea (windpipe) → splits into two bronchi (one per lung) → branches into progressively smaller bronchioles → finally reaches the alveoli — tiny air sacs where gas exchange occurs. The respiratory tract is lined with a mucociliary escalator — mucus-secreting cells trap dust and bacteria, and hair-like cilia (tiny projections) sweep the mucus upward to be swallowed or coughed out. This is the lung's first line of defence against infection. Smoking paralyses the cilia — one reason smokers are so prone to chest infections.

Breathing is powered by pressure differences — air always flows from high pressure to low pressure, just as it does when you open a fizzy drink bottle. Inhalation (breathing in) — active process: 1. The diaphragm (a dome-shaped muscle below the lungs) contracts and flattens downward 2. The external intercostal muscles (between the ribs) contract, lifting the rib cage upward and outward 3. The chest cavity volume INCREASES 4. Lung volume increases → pressure inside the lungs FALLS below atmospheric pressure 5. Air rushes IN (from high pressure outside to low pressure inside) Exhalation (breathing out) — passive at rest: 1. The diaphragm and intercostal muscles RELAX 2. The elastic recoil of the lungs (like a stretched rubber band releasing) pulls the chest wall inward 3. Lung volume DECREASES → pressure inside rises above atmospheric 4. Air rushes OUT During forced exhalation (like blowing out candles) or exercise, the internal intercostal muscles and abdominal muscles actively contract to push air out faster. Key volumes: - Tidal volume (TV) — the amount of air breathed in or out in a normal resting breath: ~500 mL - Vital capacity (VC) — the maximum air you can exhale after a maximum inhalation: ~4–5 L - Residual volume — air remaining in the lungs after maximal exhalation: ~1.2 L (lungs never fully empty — this prevents alveoli from collapsing) Spirometry measures these volumes and is used clinically to diagnose lung diseases: - Obstructive pattern (asthma, COPD) — airways are narrowed; difficult to exhale; FEV₁/FVC ratio falls - Restrictive pattern (pulmonary fibrosis) — lungs are stiff; total capacity is reduced

The alveoli are where the magic happens — where oxygen enters the blood and carbon dioxide leaves it. The alveolar design is an engineering masterpiece, perfectly optimised for rapid gas exchange. Why alveoli are so effective: 1. Enormous surface area — ~480 million alveoli in two lungs give a total gas exchange surface of ~70 m² — roughly the area of a tennis court, folded into your chest 2. Ultra-thin walls — the alveolar wall and the adjacent capillary wall together are just 0.5 micrometres thick — so thin that gases barely need to travel at all 3. Rich capillary network — each alveolus is surrounded by a basket of capillaries; virtually no alveolar surface is far from blood 4. Large concentration gradients — oxygen is abundant in fresh air (high pO₂) and depleted in blood arriving from the tissues (low pO₂) → O₂ diffuses rapidly INTO blood. CO₂ is abundant in venous blood and scarce in fresh air → CO₂ diffuses rapidly OUT. Gas exchange works entirely by diffusion — no energy required. Gases simply move down their concentration gradients across the thin membrane. What disrupts gas exchange? - Pneumonia — alveoli fill with fluid and pus → gases cannot diffuse across the liquid barrier - Pulmonary oedema (heart failure) — fluid from failing heart backs up into alveoli - Pulmonary fibrosis — alveolar walls thicken with scar tissue → diffusion distance increases → gas exchange slows - Pulmonary embolism — clot blocks blood flow to part of the lung → that area is ventilated but not perfused → "dead space" — no exchange possible

Once oxygen crosses the alveolar membrane into the blood, it cannot simply dissolve in large enough quantities — blood plasma can dissolve only about 0.3 mL of O₂ per 100 mL of blood, far too little to sustain life. Instead, almost all oxygen is carried bound to haemoglobin — a protein found inside red blood cells. Each haemoglobin molecule can carry up to 4 oxygen molecules (one on each of its four "haem" groups). One litre of blood can carry about 200 mL of oxygen when haemoglobin is fully saturated — 660× more than plasma alone. The oxygen-haemoglobin dissociation curve: Haemoglobin's affinity for oxygen changes depending on how much oxygen is already present — this is not linear but S-shaped (sigmoidal), and it is cleverly designed: - In the lungs (high pO₂ ~100 mmHg): haemoglobin binds O₂ very tightly → becomes ~98% saturated. This is what we measure as oxygen saturation (SpO₂) with a pulse oximeter. - In active tissues (low pO₂ ~40 mmHg): haemoglobin releases O₂ readily → oxygen delivered where it's needed The curve shifts to release more O₂ in conditions where tissues need more: - High CO₂ (acidic environment from active metabolism) → haemoglobin releases O₂ more readily (Bohr effect) - High temperature (exercising muscle) → more O₂ released - Low pH (acidosis) → more O₂ released This is beautiful physiological design — exercising muscles produce CO₂, heat, and acid, all of which signal haemoglobin to deliver more oxygen right where the demand is highest. Carbon dioxide transport: CO₂ travels back from tissues to the lungs in three ways: 1. Dissolved in plasma (~10%) 2. Bound to haemoglobin as carbaminohaemoglobin (~20%) 3. As bicarbonate ions (HCO₃⁻) in plasma (~70%) — CO₂ reacts with water inside red blood cells to form bicarbonate and H⁺ (carbonic anhydrase reaction). This is also how the body regulates blood pH.

Breathing is unusual among vital functions — it can be both automatic (you don't have to think about it to stay alive) and voluntary (you can choose to breathe faster, slower, or hold your breath). The respiratory control centre: Located in the medulla oblongata (the lower part of the brainstem), groups of neurons called the dorsal respiratory group and ventral respiratory group set the rhythm of breathing — sending regular signals to the diaphragm and intercostal muscles. What drives the breathing rate? The most powerful stimulus to breathe is not low oxygen — it is rising CO₂ (more precisely, the fall in blood pH that rising CO₂ causes). Central chemoreceptors in the medulla are bathed in cerebrospinal fluid (CSF). When blood CO₂ rises, CO₂ diffuses into the CSF, lowers its pH, and the chemoreceptors detect this → immediate increase in breathing rate and depth to blow off the excess CO₂. Peripheral chemoreceptors in the aortic arch and carotid bodies primarily detect falling oxygen levels (hypoxia). These kick in when oxygen drops significantly (SpO₂ below ~90%). This has a critical clinical implication: In patients with chronic lung disease (like COPD) who chronically retain CO₂, the central chemoreceptors become desensitised to high CO₂ over time. These patients rely on their peripheral chemoreceptors (detecting low oxygen) as their main drive to breathe — called the hypoxic drive. If you give them too much supplemental oxygen, you remove this drive → they may stop breathing. This is why oxygen must be given carefully and at controlled concentrations in COPD patients. Voluntary control: The cortex (thinking brain) can override the automatic breathing rhythm — which is how you hold your breath, speak, sing, or blow out candles. However, as CO₂ builds up during breath-holding, the involuntary drive eventually overwhelms the voluntary suppression — you cannot hold your breath until you lose consciousness (in healthy people under normal conditions).

Understanding respiratory physiology makes the pathology of lung disease immediately comprehensible. Asthma: The airways are chronically inflamed and hyper-reactive. During an attack, smooth muscle in the bronchioles contracts (bronchospasm) and mucus production increases → airways narrow → airflow resistance increases dramatically → patient has to work hard to breathe out (exhalation is worst because airways naturally narrow during exhalation). Treatment: bronchodilators (relax smooth muscle), corticosteroids (reduce inflammation). COPD (Chronic Obstructive Pulmonary Disease): Caused almost entirely by smoking. Two processes: 1. Chronic bronchitis — chronic inflammation and excess mucus → narrowed airways 2. Emphysema — destruction of alveolar walls → loss of surface area for gas exchange AND loss of elastic recoil → air trapping (air cannot be fully exhaled) COPD is progressive and irreversible — management aims to slow progression (stop smoking) and manage symptoms. Pneumonia: Infection fills alveoli with inflammatory fluid (exudate) → impaired gas exchange → low blood oxygen (hypoxia) → patient breathless and may need oxygen therapy. The affected lung area shows as white ("consolidation") on a chest X-ray. Pulmonary embolism (PE): A blood clot (usually from a deep vein thrombosis in the legs) travels to the lungs and blocks a pulmonary artery → that lung area is ventilated but not perfused (no blood to exchange with) → V/Q mismatch → sudden breathlessness, chest pain, and low oxygen. Treated with anticoagulants (blood thinners). Pulse oximetry and arterial blood gases: - A pulse oximeter (the clip on the finger) measures oxygen saturation (SpO₂) non-invasively. Normal >95%. - Arterial blood gases (ABG) are a blood test measuring pO₂, pCO₂, and pH directly. The gold standard for assessing respiratory failure and acid-base balance.