The Respiratory System

The respiratory system exchanges oxygen and carbon dioxide between the blood and the environment. It is anatomically divided into the upper airway (nose, pharynx, larynx) and lower airway (trachea, bronchi, bronchioles, alveoli).

Air is filtered, warmed, and humidified in the nasal passages before passing through the pharynx and larynx into the trachea. The trachea bifurcates at the carina into left and right primary bronchi, which branch progressively until they form the alveolar ducts and alveoli — the site of gas exchange. Type I pneumocytes (flat, ~95% of alveolar surface area) provide the thin diffusion barrier. Type II pneumocytes produce pulmonary surfactant, a phospholipid mixture that reduces alveolar surface tension, preventing alveolar collapse on expiration (Laplace's law: P = 2T/r). Surfactant deficiency in preterm infants causes respiratory distress syndrome.

Breathing is driven by pressure gradients. The diaphragm (phrenic nerve, C3–C5) contracts on inspiration, increasing thoracic volume and lowering intrapleural pressure from −5 to −8 cmH2O. By Boyle's law, alveolar pressure falls below atmospheric and air flows in. Expiration is passive at rest — elastic recoil raises alveolar pressure above atmospheric. Lung compliance (ΔV/ΔP) is reduced in pulmonary fibrosis and increased in emphysema.

Lung volumes measured by spirometry include tidal volume (TV ~500 mL), inspiratory reserve volume (IRV), expiratory reserve volume (ERV), and residual volume (RV). FEV1/FVC <0.70 defines obstructive lung disease (asthma, COPD); reduced FVC with normal ratio indicates restrictive disease (fibrosis, effusion). Dead space is the volume of the respiratory tract that does not participate in gas exchange. Anatomical dead space (~150 mL) comprises the conducting airways. Alveolar dead space arises where alveoli are ventilated but not perfused. Total (physiological) dead space = anatomical + alveolar dead space.

The ventilation-perfusion (V/Q) ratio is ideally 1.0. V/Q mismatch is the commonest cause of hypoxaemia. In a pulmonary embolism (dead space: V/Q → ∞) ventilation is wasted. In lobar pneumonia (shunt: V/Q → 0) blood passes unventilated alveoli and is not oxygenated. Lung compliance determines how easily the lung stretches; low compliance increases the work of breathing.

Gas exchange follows Fick's law: rate ∝ (surface area × partial pressure gradient) / (thickness × diffusion distance). Alveolar PO2 is ~104 mmHg; mixed venous PO2 ~40 mmHg. This gradient drives oxygen diffusion into pulmonary capillary blood. CO2 diffuses in the opposite direction driven by its own gradient (~46 vs 40 mmHg).

Oxygen is transported 98% bound to haemoglobin and 2% dissolved in plasma. The haemoglobin-oxygen dissociation curve is sigmoidal due to cooperative binding. A rightward shift (decreased O2 affinity, enhanced unloading) occurs with increased CO2, H+, temperature, and 2,3-BPG — all elevated in metabolically active tissues (the Bohr effect). A leftward shift (increased affinity) is caused by alkalosis, hypothermia, and fetal haemoglobin (HbF), which allows placental oxygen transfer.

Carbon dioxide is transported as bicarbonate (~70%), carbamino compounds (~25%), and dissolved CO2 (~5%). In tissue capillaries, carbonic anhydrase in red blood cells catalyses: CO2 + H2O → H2CO3 → H+ + HCO3−. Bicarbonate is exported via the chloride shift. H+ is buffered by deoxygenated haemoglobin (Haldane effect). The Henderson-Hasselbalch equation (pH = 6.1 + log [HCO3−]/0.03×PCO2) governs acid-base balance.

Central chemoreceptors in the medulla respond primarily to changes in PCO2/pH of cerebrospinal fluid. Peripheral chemoreceptors (carotid and aortic bodies) respond to hypoxaemia (PO2 <60 mmHg), hypercapnia, and acidosis, providing a secondary ventilatory drive.